3kpe - Revision history

OCA at 08:20, 6 September 2023

2023-09-06T08:20:02Z

←Older revision		Revision as of 08:20, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3kpe' size='340' side='right'caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='3kpe' size='340' side='right'caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human_respiratory_syncytial_virus~~ Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=3KPE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_A2 Human respiratory syncytial virus A2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KPE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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]] 1.47Å</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [~~http~~://pdbe.org/3kpe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3kpe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3kpe ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [https://pdbe.org/3kpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [https://www.ebi.ac.uk/pdbsum/3kpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kpe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA]] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref>	+	[https://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human respiratory syncytial virus]]	+	[[Category: Human respiratory syncytial virus A2]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andries, K]]	+	[[Category: Andries K]]
-	[[Category: Arnoult, E]]	+	[[Category: Arnoult E]]
-	[[Category: ~~Bondt, H De~~]]	+	[[Category: Cummings MD]]
-	[[Category: ~~Cummings, M D~~]]	+	[[Category: De Bondt H]]
-	[[Category: Roymans, D]]	+	[[Category: Roymans D]]
-	[[Category: Vlijmen, H ~~Van]]~~	+	[[Category: Van Vlijmen H]]
-	~~[[Category: Alpha helix]]~~	+
-	~~[[Category: Coiled-coil]]~~	+
-	~~[[Category: Envelope protein]]~~	+
-	~~[[Category: Fusion protein]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Host cell membrane]]~~	+
-	~~[[Category: Host membrane]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Palmitate]]~~	+
-	~~[[Category: Peptide-small-molecule complex]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Viral protein]]~~	+
-	~~[[Category: Virion~~]]	+

OCA at 07:02, 7 October 2020

2020-10-07T07:02:54Z

←Older revision		Revision as of 07:02, 7 October 2020
Line 1:		Line 1:

	==Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV==		==Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV==
-	<StructureSection load='3kpe' size='340' side='right' caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>	+	<StructureSection load='3kpe' size='340' side='right'caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3KPE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3KPE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://pdbe.org/3kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kpe ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://pdbe.org/3kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kpe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 33:		Line 33:
	</StructureSection>		</StructureSection>
	[[Category: Human respiratory syncytial virus]]		[[Category: Human respiratory syncytial virus]]
		+	[[Category: Large Structures]]
	[[Category: Andries, K]]		[[Category: Andries, K]]
	[[Category: Arnoult, E]]		[[Category: Arnoult, E]]

OCA at 09:23, 26 December 2018

2018-12-26T09:23:25Z

←Older revision		Revision as of 09:23, 26 December 2018
Line 1:		Line 1:
		+
	==Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV==		==Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV==
	<StructureSection load='3kpe' size='340' side='right' caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='3kpe' size='340' side='right' caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KPE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KPE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://pdbe.org/3kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe 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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://pdbe.org/3kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kpe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 12:		Line 13:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kp/3kpe_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kp/3kpe_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>

OCA at 13:31, 9 February 2016

2016-02-09T13:31:20Z

←Older revision		Revision as of 13:31, 9 February 2016
Line 4:		Line 4:
	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KPE FirstGlance]. <br>		<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KPE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe 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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://pdbe.org/3kpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 16:
	<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=3kpe ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 26:		Line 26:
	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 3kpe" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:06, 25 December 2014

2014-12-25T07:06:31Z

←Older revision		Revision as of 07:06, 25 December 2014
Line 6:		Line 6:
	<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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe 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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA]] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 15:14, 18 December 2014

2014-12-18T15:14:48Z

←Older revision		Revision as of 15:14, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3kpe\| PDB=3kpe \| SCENE= }}~~	+	==Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV==
-	===Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV===	+	<StructureSection load='3kpe' size='340' side='right' caption='[[3kpe]], [[Resolution\|resolution]] 1.47Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19966279}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KPE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TM3:2-[[6-[[[2-(3-HYDROXYPROPYL)-5-METHYLPHENYL]AMINO]METHYL]-2-[[3-(4-MORPHOLINYL)PROPYL]AMINO]-1H-BENZIMIDAZOL-1-YL]METHYL]-6-METHYL-3-PYRIDINOL'>TM3</scene></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=3kpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kpe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kpe RCSB], [http://www.ebi.ac.uk/pdbsum/3kpe 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/kp/3kpe_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 ==
		+	Six-helix bundle (6HB) formation is an essential step for many viruses that rely on a class I fusion protein to enter a target cell and initiate replication. Because the binding modes of small molecule inhibitors of 6HB formation are largely unknown, precisely how they disrupt 6HB formation remains unclear, and structure-based design of improved inhibitors is thus seriously hampered. Here we present the high resolution crystal structure of TMC353121, a potent inhibitor of respiratory syncytial virus (RSV), bound at a hydrophobic pocket of the 6HB formed by amino acid residues from both HR1 and HR2 heptad-repeats. Binding of TMC353121 stabilizes the interaction of HR1 and HR2 in an alternate conformation of the 6HB, in which direct binding interactions are formed between TMC353121 and both HR1 and HR2. Rather than completely preventing 6HB formation, our data indicate that TMC353121 inhibits fusion by causing a local disturbance of the natural 6HB conformation.

-	~~==Function==~~	+	Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein.,Roymans D, De Bondt HL, Arnoult E, Geluykens P, Gevers T, Van Ginderen M, Verheyen N, Kim H, Willebrords R, Bonfanti JF, Bruinzeel W, Cummings MD, van Vlijmen H, Andries K Proc Natl Acad Sci U S A. 2009 Dec 4. PMID:19966279<ref>PMID:19966279</ref>
-	[[http://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA]] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a ~~trimer~~-of-~~hairpins structure, positioning the fusion peptide in close proximity to the C~~-~~terminal region~~ of the ~~ectodomain. The formation of this structure appears to drive apposition and subsequent~~ fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein ~~F) interacts with glycoprotein G at the virion surface~~. ~~Upon binding of G to heparan sulfate~~, ~~the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane~~, ~~inducing the fusion between host cell and virion membranes. Notably~~, ~~RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore~~, ~~the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection~~, ~~proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia~~, ~~a cytopathic effect that could lead to tissue necrosis~~. ~~The fusion protein is also able to trigger p53-dependent apoptosis~~.~~<ref>~~PMID:~~12663767</ref>~~ <ref>PMID:~~18216092~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3kpe]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:019966279</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Human respiratory syncytial virus]]		[[Category: Human respiratory syncytial virus]]
-	[[Category: Andries, K.]]	+	[[Category: Andries, K]]
-	[[Category: Arnoult, E.]]	+	[[Category: Arnoult, E]]
-	[[Category: Bondt, H De.]]	+	[[Category: Bondt, H De]]
-	[[Category: Cummings, M D.]]	+	[[Category: Cummings, M D]]
-	[[Category: Roymans, D.]]	+	[[Category: Roymans, D]]
-	[[Category: Vlijmen, H Van.]]	+	[[Category: Vlijmen, H Van]]
	[[Category: Alpha helix]]		[[Category: Alpha helix]]
	[[Category: Coiled-coil]]		[[Category: Coiled-coil]]

OCA: Protected "3kpe" [edit=sysop:move=sysop]

2013-04-04T02:07:04Z

Protected "3kpe" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:07, 4 April 2013

OCA at 02:07, 4 April 2013

2013-04-04T02:07:01Z

←Older revision		Revision as of 02:07, 4 April 2013
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-	{{Seed}}
-	[[Image:3kpe.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3kpe", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
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	{{STRUCTURE_3kpe\| PDB=3kpe \| SCENE= }}		{{STRUCTURE_3kpe\| PDB=3kpe \| SCENE= }}
-
	===Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV===		===Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV===
		+	{{ABSTRACT_PUBMED_19966279}}

-		+	==Function==
-	<!--	+	[[http://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA]] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref>
-	~~The line below this paragraph~~, ~~{{ABSTRACT_PUBMED_19966279}}~~, ~~adds~~ the ~~Publication Abstract~~ to the ~~page~~	+
-	~~(as it~~ appears ~~on PubMed at http://www~~.~~pubmed~~.~~gov~~), ~~where 19966279~~ is the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_19966279}}~~	+

	==About this Structure==		==About this Structure==
-	~~3KPE~~ is a 2 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/~~Human_respiratory_syncytial_virus_a2~~ Human respiratory syncytial virus a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA].	+	[[3kpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19966279~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019966279</ref><references group="xtra"/><references/>
-	[[Category: Human respiratory syncytial virus a2]]	+	[[Category: Human respiratory syncytial virus]]
	[[Category: Andries, K.]]		[[Category: Andries, K.]]
	[[Category: Arnoult, E.]]		[[Category: Arnoult, E.]]
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	[[Category: Membrane]]		[[Category: Membrane]]
	[[Category: Palmitate]]		[[Category: Palmitate]]
-	[[Category: Peptide/small-molecule complex]]	+	[[Category: Peptide-small-molecule complex]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
		+	[[Category: Viral protein]]
	[[Category: Virion]]		[[Category: Virion]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 3 08:53:55 2010''

OCA at 06:53, 3 February 2010

2010-02-03T06:53:56Z

←Older revision		Revision as of 06:53, 3 February 2010
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-	[[Image:3kpe.~~jpg~~\|left\|200px]]	+	[[Image:3kpe.png\|left\|200px]]

	<!--		<!--
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	==About this Structure==		==About this Structure==
-	3KPE is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_a2 Human respiratory syncytial virus a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA].	+	3KPE is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_a2 Human respiratory syncytial virus a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KPE OCA].

	==Reference==		==Reference==
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	[[Category: Virion]]		[[Category: Virion]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Dec 24 07~~:31:~~01 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 3 08:53:55 2010''

OCA at 05:31, 24 December 2009

2009-12-24T05:31:02Z

←Older revision		Revision as of 05:31, 24 December 2009
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	===Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV===		===Solution structure of the respiratory syncytial virus (RSV)six-helix bundle complexed with TMC353121, a small-moleucule inhibitor of RSV===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19966279}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19966279 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19966279}}

	==About this Structure==		==About this Structure==
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	[[Category: Virion]]		[[Category: Virion]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Dec ~~23 09~~:44:29 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Dec 24 07:31:01 2009''