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| | ==Crystal Structure of the Rhesus Rotavirus VP5 Antigen Domain Trimer== | | ==Crystal Structure of the Rhesus Rotavirus VP5 Antigen Domain Trimer== |
| - | <StructureSection load='2b4i' size='340' side='right' caption='[[2b4i]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2b4i' size='340' side='right'caption='[[2b4i]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2b4i]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Rhesus_rotavirus Rhesus rotavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2B4I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2b4i]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Simian_rotavirus_A_strain_RRV Simian rotavirus A strain RRV]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B4I FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1slq|1slq]], [[2b4h|2b4h]]</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">GENOME SEGMENT 4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10969 Rhesus rotavirus])</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=2b4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b4i OCA], [https://pdbe.org/2b4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b4i RCSB], [https://www.ebi.ac.uk/pdbsum/2b4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b4i ProSAT]</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=2b4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b4i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2b4i RCSB], [http://www.ebi.ac.uk/pdbsum/2b4i PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP4_ROTRH VP4_ROTRH]] Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.<ref>PMID:20375171</ref> Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.<ref>PMID:20375171</ref> VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact.<ref>PMID:20375171</ref> | + | [https://www.uniprot.org/uniprot/VP4_ROTRH VP4_ROTRH] Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.<ref>PMID:20375171</ref> Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.<ref>PMID:20375171</ref> VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact.<ref>PMID:20375171</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/b4/2b4i_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b4/2b4i_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> |
| | </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=2b4i ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | 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 2b4i" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Virus coat protein|Virus coat protein]] | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Rhesus rotavirus]] | + | [[Category: Large Structures]] |
| - | [[Category: Dormitzer, P R]] | + | [[Category: Simian rotavirus A strain RRV]] |
| - | [[Category: Yoder, J D]] | + | [[Category: Dormitzer PR]] |
| - | [[Category: Beta sandwich]] | + | [[Category: Yoder JD]] |
| - | [[Category: Greek key]]
| + | |
| - | [[Category: Membrane penetration protein]]
| + | |
| - | [[Category: Non-enveloped virus]]
| + | |
| - | [[Category: Rearrangement]]
| + | |
| - | [[Category: Spike protein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
VP4_ROTRH Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.[1] Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.[2] VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact.[3]
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 spike protein VP4 is a key component of the membrane penetration apparatus of rotavirus, a nonenveloped virus that causes childhood gastroenteritis. Trypsin cleavage of VP4 produces a fragment, VP5*, with a potential membrane interaction region, and primes rotavirus for cell entry. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. Here, we report that a globular domain of VP5*, the VP5* antigen domain, is an autonomously folding unit that alternatively forms well-ordered dimers and trimers. Because the domain contains heterotypic neutralizing epitopes and is soluble when expressed directly, it is a promising potential subunit vaccine component. X-ray crystal structures show that the dimer resembles the spike body on trypsin-primed virions, and the trimer resembles the folded-back form of the spike. The same structural elements pack differently to form key intermolecular contacts in both oligomers. The intrinsic molecular property of alternatively forming dimers and trimers facilitates the VP5* reorganization, which is thought to mediate membrane penetration during cell entry.
Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement.,Yoder JD, Dormitzer PR EMBO J. 2006 Apr 5;25(7):1559-68. Epub 2006 Mar 2. PMID:16511559[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim IS, Trask SD, Babyonyshev M, Dormitzer PR, Harrison SC. Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry. J Virol. 2010 Jun;84(12):6200-7. doi: 10.1128/JVI.02461-09. Epub 2010 Apr 7. PMID:20375171 doi:http://dx.doi.org/10.1128/JVI.02461-09
- ↑ Kim IS, Trask SD, Babyonyshev M, Dormitzer PR, Harrison SC. Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry. J Virol. 2010 Jun;84(12):6200-7. doi: 10.1128/JVI.02461-09. Epub 2010 Apr 7. PMID:20375171 doi:http://dx.doi.org/10.1128/JVI.02461-09
- ↑ Kim IS, Trask SD, Babyonyshev M, Dormitzer PR, Harrison SC. Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry. J Virol. 2010 Jun;84(12):6200-7. doi: 10.1128/JVI.02461-09. Epub 2010 Apr 7. PMID:20375171 doi:http://dx.doi.org/10.1128/JVI.02461-09
- ↑ Yoder JD, Dormitzer PR. Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement. EMBO J. 2006 Apr 5;25(7):1559-68. Epub 2006 Mar 2. PMID:16511559
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