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- | {{Seed}} | |
- | [[Image:2hrv.png|left|200px]] | |
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- | <!-- | + | ==2A CYSTEINE PROTEINASE FROM HUMAN RHINOVIRUS 2== |
- | The line below this paragraph, containing "STRUCTURE_2hrv", creates the "Structure Box" on the page.
| + | <StructureSection load='2hrv' size='340' side='right'caption='[[2hrv]], [[Resolution|resolution]] 1.95Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2hrv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhinovirus_A2 Rhinovirus A2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HRV FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | {{STRUCTURE_2hrv| PDB=2hrv | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hrv OCA], [https://pdbe.org/2hrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hrv RCSB], [https://www.ebi.ac.uk/pdbsum/2hrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hrv ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/POLG_HRV2 POLG_HRV2] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref> |
| + | == 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/hr/2hrv_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/main_output.php?pdb_ID=2hrv ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | The crystal structure of the 2A proteinase from human rhinovirus serotype 2 (HRV2-2A(pro)) has been solved to 1.95 A resolution. The structure has an unusual, although chymotrypsin-related, fold comprising a unique four-stranded beta sheet as the N-terminal domain and a six-stranded beta barrel as the C-terminal domain. A tightly bound zinc ion, essential for the stability of HRV2-2A(pro), is tetrahedrally coordinated by three cysteine sulfurs and one histidine nitrogen. The active site consists of a catalytic triad formed by His18, Asp35 and Cys106. Asp35 is additionally involved in an extensive hydrogen-bonding network. Modelling studies reveal a substrate-induced fit that explains the specificity of the subsites S4, S2, S1 and S1'. The structure of HRV2-2A(pro) suggests the mechanism of the cis cleavage and its release from the polyprotein. |
| | | |
- | ===2A CYSTEINE PROTEINASE FROM HUMAN RHINOVIRUS 2===
| + | The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis.,Petersen JF, Cherney MM, Liebig HD, Skern T, Kuechler E, James MN EMBO J. 1999 Oct 15;18(20):5463-75. PMID:10523291<ref>PMID:10523291</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 2hrv" style="background-color:#fffaf0;"></div> |
| | | |
- | <!--
| + | ==See Also== |
- | The line below this paragraph, {{ABSTRACT_PUBMED_10523291}}, adds the Publication Abstract to the page
| + | *[[Proteinase 3D structures|Proteinase 3D structures]] |
- | (as it appears on PubMed at http://www.pubmed.gov), where 10523291 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_10523291}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | [[Category: Large Structures]] |
- | 2HRV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_rhinovirus_2 Human rhinovirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HRV OCA].
| + | [[Category: Rhinovirus A2]] |
- | | + | [[Category: Cherney MM]] |
- | ==Reference== | + | [[Category: James MNG]] |
- | The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis., Petersen JF, Cherney MM, Liebig HD, Skern T, Kuechler E, James MN, EMBO J. 1999 Oct 15;18(20):5463-75. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10523291 10523291]
| + | [[Category: Kuechler E]] |
- | [[Category: Human rhinovirus 2]] | + | [[Category: Liebig H-D]] |
- | [[Category: Picornain 2A]] | + | [[Category: Petersen JFW]] |
- | [[Category: Single protein]]
| + | [[Category: Skern T]] |
- | [[Category: Cherney, M M.]] | + | |
- | [[Category: James, M N.G.]] | + | |
- | [[Category: Kuechler, E.]] | + | |
- | [[Category: Liebig, H D.]] | + | |
- | [[Category: Petersen, J F.W.]] | + | |
- | [[Category: Skern, T.]] | + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:06:24 2008''
| + | |
| Structural highlights
Function
POLG_HRV2 Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.[1] [2] VP0 precursor is a component of immature procapsids (By similarity).[3] [4] Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.[5] [6] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[7] [8] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[9] [10] Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).[11] [12] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[13] [14] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[15] [16]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The crystal structure of the 2A proteinase from human rhinovirus serotype 2 (HRV2-2A(pro)) has been solved to 1.95 A resolution. The structure has an unusual, although chymotrypsin-related, fold comprising a unique four-stranded beta sheet as the N-terminal domain and a six-stranded beta barrel as the C-terminal domain. A tightly bound zinc ion, essential for the stability of HRV2-2A(pro), is tetrahedrally coordinated by three cysteine sulfurs and one histidine nitrogen. The active site consists of a catalytic triad formed by His18, Asp35 and Cys106. Asp35 is additionally involved in an extensive hydrogen-bonding network. Modelling studies reveal a substrate-induced fit that explains the specificity of the subsites S4, S2, S1 and S1'. The structure of HRV2-2A(pro) suggests the mechanism of the cis cleavage and its release from the polyprotein.
The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis.,Petersen JF, Cherney MM, Liebig HD, Skern T, Kuechler E, James MN EMBO J. 1999 Oct 15;18(20):5463-75. PMID:10523291[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
- ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
- ↑ Petersen JF, Cherney MM, Liebig HD, Skern T, Kuechler E, James MN. The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis. EMBO J. 1999 Oct 15;18(20):5463-75. PMID:10523291 doi:10.1093/emboj/18.20.5463
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