3dox - Revision history

OCA at 19:20, 29 May 2024

2024-05-29T19:20:26Z

←Older revision		Revision as of 19:20, 29 May 2024
Line 3:		Line 3:
	<StructureSection load='3dox' size='340' side='right'caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3dox' size='340' side='right'caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hiv~~-~~1 Hiv~~-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV-1_M:B_HXB2R HIV-1 M:B_HXB2R]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOX FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</div></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">gag-pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=11706 HIV-1])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [https://pdbe.org/3dox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [https://www.ebi.ac.uk/pdbsum/3dox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dox ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [https://pdbe.org/3dox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [https://www.ebi.ac.uk/pdbsum/3dox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dox ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>	+	[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 39:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: HIV-1 ~~retropepsin]]~~	+	[[Category: HIV-1 M:B_HXB2R]]
-	~~[[Category~~: ~~Hiv-1~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bihani, S]]	+	[[Category: Bihani S]]
-	[[Category: Das, A]]	+	[[Category: Das A]]
-	[[Category: Ferrer, J L]]	+	[[Category: Ferrer J-L]]
-	[[Category: Hosur~~, M V~~]]	+	[[Category: Hosur MV]]
-	[[Category: Prashar, V]]	+	[[Category: Prashar V]]
-	~~[[Category: Aid]]~~	+
-	~~[[Category: Aspartyl protease]]~~	+
-	~~[[Category: Capsid maturation]]~~	+
-	~~[[Category: Capsid protein]]~~	+
-	~~[[Category: Catalysis]]~~	+
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Dna integration]]~~	+
-	~~[[Category: Dna recombination]]~~	+
-	~~[[Category: Dna-directed dna polymerase]]~~	+
-	~~[[Category: Endonuclease]]~~	+
-	~~[[Category: Hiv-1 protease]]~~	+
-	~~[[Category: Host-virus interaction]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Magnesium]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Multifunctional enzyme]]~~	+
-	~~[[Category: Myristate]]~~	+
-	~~[[Category: Nuclease]]~~	+
-	~~[[Category: Nucleotidyltransferase]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Protease]]~~	+
-	~~[[Category: Reaction intermediate]]~~	+
-	~~[[Category: Ribosomal frameshifting]]~~	+
-	~~[[Category: Rna-binding]]~~	+
-	~~[[Category: Rna-directed dna polymerase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transition state]]~~	+
-	~~[[Category: Viral nucleoprotein]]~~	+
-	~~[[Category: Virion]]~~	+
-	~~[[Category: X-ray crystallography]]~~	+
-	~~[[Category: Zinc]]~~	+
-	~~[[Category: Zinc-finger~~]]	+

OCA at 07:33, 10 November 2021

2021-11-10T07:33:27Z

←Older revision		Revision as of 07:33, 10 November 2021
Line 1:		Line 1:

	==X-ray structure of HIV-1 protease in situ product complex==		==X-ray structure of HIV-1 protease in situ product complex==
-	<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='3dox' size='340' side='right'caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3DOX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOX FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [~~http~~://pdbe.org/3dox PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3dox PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3dox ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [https://pdbe.org/3dox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [https://www.ebi.ac.uk/pdbsum/3dox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dox ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>	+	[[https://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/3dox_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/3dox_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 32:		Line 32:

	==See Also==		==See Also==
		+	*[[Immunodeficiency virus protease 3D structures\|Immunodeficiency virus protease 3D structures]]
	*[[Kink-turn motif\|Kink-turn motif]]		*[[Kink-turn motif\|Kink-turn motif]]
	*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]		*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]
Line 40:		Line 41:
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Hiv-1]]		[[Category: Hiv-1]]
		+	[[Category: Large Structures]]
	[[Category: Bihani, S]]		[[Category: Bihani, S]]
	[[Category: Das, A]]		[[Category: Das, A]]

OCA at 11:28, 7 October 2017

2017-10-07T11:28:46Z

←Older revision		Revision as of 11:28, 7 October 2017
Line 1:		Line 1:
		+
	==X-ray structure of HIV-1 protease in situ product complex==		==X-ray structure of HIV-1 protease in situ product complex==
	<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 6:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://pdbe.org/3dox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://pdbe.org/3dox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dox ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 33:		Line 34:
	*[[Kink-turn motif\|Kink-turn motif]]		*[[Kink-turn motif\|Kink-turn motif]]
	*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]		*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]
-	*[[Virus protease\|Virus protease]]
	== References ==		== References ==
	<references/>		<references/>
Line 50:		Line 50:
	[[Category: Capsid protein]]		[[Category: Capsid protein]]
	[[Category: Catalysis]]		[[Category: Catalysis]]
		+	[[Category: Cytoplasm]]
	[[Category: Dna integration]]		[[Category: Dna integration]]
	[[Category: Dna recombination]]		[[Category: Dna recombination]]
Line 69:		Line 70:
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Reaction intermediate]]		[[Category: Reaction intermediate]]
		+	[[Category: Ribosomal frameshifting]]
	[[Category: Rna-binding]]		[[Category: Rna-binding]]
	[[Category: Rna-directed dna polymerase]]		[[Category: Rna-directed dna polymerase]]
Line 76:		Line 78:
	[[Category: Virion]]		[[Category: Virion]]
	[[Category: X-ray crystallography]]		[[Category: X-ray crystallography]]
		+	[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

OCA at 00:33, 8 February 2016

2016-02-08T00:33:10Z

←Older revision		Revision as of 00:33, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-~~1_m:b_hxb2r~~ Hiv-1 ~~m:b_hxb2r~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DOX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DOX FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1 ~~M:B_HXB2R~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://pdbe.org/3dox PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3dox ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		Line 28:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3dox" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
-	[[Category: Hiv-1 ~~m:b_hxb2r~~]]	+	[[Category: Hiv-1]]
	[[Category: Bihani, S]]		[[Category: Bihani, S]]
	[[Category: Das, A]]		[[Category: Das, A]]

OCA at 19:16, 24 December 2014

2014-12-24T19:16:25Z

←Older revision		Revision as of 19:16, 24 December 2014
Line 8:		Line 8:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POL_HV1H2 POL_HV1H2]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref> Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.<ref>PMID:8648689</ref> <ref>PMID:17041220</ref> <ref>PMID:17070549</ref> <ref>PMID:20554775</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 14:07, 17 December 2014

2014-12-17T14:07:21Z

←Older revision		Revision as of 14:07, 17 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3dox\| PDB=3dox \| SCENE= }}~~	+	==X-ray structure of HIV-1 protease in situ product complex==
-	===X-ray structure of HIV-1 protease in situ product complex===	+	<StructureSection load='3dox' size='340' side='right' caption='[[3dox]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_18704947}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3dox]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1_m:b_hxb2r Hiv-1 m:b_hxb2r]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DOX FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1g6l\|1g6l]], [[1lv1\|1lv1]], [[2nph\|2nph]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11706 HIV-1 M:B_HXB2R])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dox OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dox RCSB], [http://www.ebi.ac.uk/pdbsum/3dox PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/3dox_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	HIV-1 protease is an effective target for design of different types of drugs against AIDS. HIV-1 protease is also one of the few enzymes that can cleave substrates containing both proline and nonproline residues at the cleavage site. We report here the first structure of HIV-1 protease complexed with the product peptides SQNY and PIV derived by in situ cleavage of the oligopeptide substrate SQNYPIV, within the crystals. In the structure, refined against 2.0-A resolution synchrotron data, a carboxyl oxygen of SQNY is hydrogen-bonded with the N-terminal nitrogen atom of PIV. At the same time, this proline nitrogen atom does not form any hydrogen bond with catalytic aspartates. These two observations suggest that the protonation of scissile nitrogen, during peptide bond cleavage, is by a gem-hydroxyl of the tetrahedral intermediate rather than by a catalytic aspartic acid. Proteins 2008. (c) 2008 Wiley-Liss, Inc.

-	~~==About this Structure==~~	+	X-ray structure of HIV-1 protease in situ product complex.,Bihani S, Das A, Prashar V, Ferrer JL, Hosur MV Proteins. 2008 Aug 14. PMID:18704947<ref>PMID:18704947</ref>
-	~~[[3dox]] is a 3 chain~~ structure ~~with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Hiv-1_m~~:~~b_hxb2r Hiv-1 m:b_hxb2r]. Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=3DOX OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
Line 10:		Line 31:
	*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]		*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]
	*[[Virus protease\|Virus protease]]		*[[Virus protease\|Virus protease]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:018704947<~~/~~ref~~><~~ref group="xtra">PMID:011170214</ref><ref group="xtra">PMID:015794743</ref><ref group="xtra">PMID:014993705</ref><references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Hiv-1 m:b_hxb2r]]		[[Category: Hiv-1 m:b_hxb2r]]
-	[[Category: Bihani, S.]]	+	[[Category: Bihani, S]]
-	[[Category: Das, A.]]	+	[[Category: Das, A]]
-	[[Category: Ferrer, J L.]]	+	[[Category: Ferrer, J L]]
-	[[Category: Hosur, M V.]]	+	[[Category: Hosur, M V]]
-	[[Category: Prashar, V.]]	+	[[Category: Prashar, V]]
	[[Category: Aid]]		[[Category: Aid]]
	[[Category: Aspartyl protease]]		[[Category: Aspartyl protease]]

OCA at 10:54, 11 March 2013

2013-03-11T10:54:51Z

←Older revision		Revision as of 10:54, 11 March 2013
Line 1:		Line 1:
-	[[Image:3dox.png\|left\|200px]]
-
	{{STRUCTURE_3dox\| PDB=3dox \| SCENE= }}		{{STRUCTURE_3dox\| PDB=3dox \| SCENE= }}
-
	===X-ray structure of HIV-1 protease in situ product complex===		===X-ray structure of HIV-1 protease in situ product complex===
-
	{{ABSTRACT_PUBMED_18704947}}		{{ABSTRACT_PUBMED_18704947}}

OCA at 08:18, 20 October 2012

2012-10-20T08:18:43Z

←Older revision		Revision as of 08:18, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3dox]] is a 3 chain structure ~~of [[Kink-turn motif]], [[User:Wayne Decatur/kink-turn motif]] and [[Virus protease]]~~ with sequence from [http://en.wikipedia.org/wiki/~~Human_immunodeficiency_virus_type_1_(isolate_hxb2_group_m_subtype_b) Human immunodeficiency virus type~~ 1 ~~(isolate hxb2 group~~ m ~~subtype b)~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].	+	[[3dox]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1_m:b_hxb2r Hiv-1 m:b_hxb2r]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].

	==See Also==		==See Also==
Line 16:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:018704947</ref><ref group="xtra">PMID:011170214</ref><ref group="xtra">PMID:015794743</ref><ref group="xtra">PMID:014993705~~</ref><ref group="xtra">PMID:017116869~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018704947</ref><ref group="xtra">PMID:011170214</ref><ref group="xtra">PMID:015794743</ref><ref group="xtra">PMID:014993705</ref><references group="xtra"/>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
		+	[[Category: Hiv-1 m:b_hxb2r]]
	[[Category: Bihani, S.]]		[[Category: Bihani, S.]]
	[[Category: Das, A.]]		[[Category: Das, A.]]

OCA at 19:07, 25 July 2012

2012-07-25T19:07:48Z

←Older revision		Revision as of 19:07, 25 July 2012
Line 1:		Line 1:
	[[Image:3dox.png\|left\|200px]]		[[Image:3dox.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3dox", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3dox\| PDB=3dox \| SCENE= }}		{{STRUCTURE_3dox\| PDB=3dox \| SCENE= }}

	===X-ray structure of HIV-1 protease in situ product complex===		===X-ray structure of HIV-1 protease in situ product complex===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18704947}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18704947 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_18704947}}		{{ABSTRACT_PUBMED_18704947}}

	==About this Structure==		==About this Structure==
-	[[3dox]] is a 3 chain structure of [[User:Wayne Decatur/kink-turn motif]] with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_hxb2_group_m_subtype_b) Human immunodeficiency virus type 1 (isolate hxb2 group m subtype b)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].	+	[[3dox]] is a 3 chain structure of [[Kink-turn motif]], [[User:Wayne Decatur/kink-turn motif]] and [[Virus protease]] with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_hxb2_group_m_subtype_b) Human immunodeficiency virus type 1 (isolate hxb2 group m subtype b)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].

	==See Also==		==See Also==
-	*[[User:Wayne Decatur/kink-turn motif]]	+	*[[Kink-turn motif\|Kink-turn motif]]
		+	*[[User:Wayne Decatur/kink-turn motif\|User:Wayne Decatur/kink-turn motif]]
		+	*[[Virus protease\|Virus protease]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18704947~~</ref><ref group="xtra">PMID:~~11170214~~</ref><ref group="xtra">PMID:~~15794743~~</ref><ref group="xtra">PMID:~~14993705~~</ref><ref group="xtra">PMID:~~17116869~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018704947</ref><ref group="xtra">PMID:011170214</ref><ref group="xtra">PMID:015794743</ref><ref group="xtra">PMID:014993705</ref><ref group="xtra">PMID:017116869</ref><references group="xtra"/>
	[[Category: HIV-1 retropepsin]]		[[Category: HIV-1 retropepsin]]
	[[Category: Bihani, S.]]		[[Category: Bihani, S.]]
Line 37:		Line 28:
	[[Category: Capsid protein]]		[[Category: Capsid protein]]
	[[Category: Catalysis]]		[[Category: Catalysis]]
-	[[Category: Cytoplasm]]
	[[Category: Dna integration]]		[[Category: Dna integration]]
	[[Category: Dna recombination]]		[[Category: Dna recombination]]
Line 57:		Line 47:
	[[Category: Protease]]		[[Category: Protease]]
	[[Category: Reaction intermediate]]		[[Category: Reaction intermediate]]
-	[[Category: Ribosomal frameshifting]]
	[[Category: Rna-binding]]		[[Category: Rna-binding]]
	[[Category: Rna-directed dna polymerase]]		[[Category: Rna-directed dna polymerase]]
Line 65:		Line 54:
	[[Category: Virion]]		[[Category: Virion]]
	[[Category: X-ray crystallography]]		[[Category: X-ray crystallography]]
-	[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

OCA at 23:32, 14 March 2011

2011-03-14T23:32:06Z

←Older revision		Revision as of 23:32, 14 March 2011
Line 19:		Line 19:

	==About this Structure==		==About this Structure==
-	[[3dox]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_hxb2_group_m_subtype_b) Human immunodeficiency virus type 1 (isolate hxb2 group m subtype b)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].	+	[[3dox]] is a 3 chain structure of [[User:Wayne Decatur/kink-turn motif]] with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(isolate_hxb2_group_m_subtype_b) Human immunodeficiency virus type 1 (isolate hxb2 group m subtype b)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOX OCA].

	==See Also==		==See Also==