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| | <StructureSection load='4yfw' size='340' side='right'caption='[[4yfw]], [[Resolution|resolution]] 1.66Å' scene=''> | | <StructureSection load='4yfw' size='340' side='right'caption='[[4yfw]], [[Resolution|resolution]] 1.66Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yfw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Group_a_rotaviruses Group a rotaviruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YFW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YFW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yfw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rotavirus_A Rotavirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YFW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4drv|4drv]], [[4ye2|4ye2]], [[4yfz|4yfz]], [[4yg0|4yg0]], [[4yg3|4yg3]], [[4yg6|4yg6]]</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]] 1.66Å</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=4yfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yfw OCA], [http://pdbe.org/4yfw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yfw RCSB], [http://www.ebi.ac.uk/pdbsum/4yfw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yfw 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=4yfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yfw OCA], [https://pdbe.org/4yfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yfw RCSB], [https://www.ebi.ac.uk/pdbsum/4yfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yfw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/B6RGK2_9REOV B6RGK2_9REOV]] 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 (By similarity).[SAAS:SAAS00209906] 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 (By similarity).[SAAS:SAAS00209911] | + | [https://www.uniprot.org/uniprot/B6RGK2_9VIRU B6RGK2_9VIRU] Outer capsid protein VP4: 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. 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. It is subsequently lost, together with VP7, following virus entry into the host cell. Following entry into the host cell, low intracellular or intravesicular Ca(2+) concentration probably causes the calcium-stabilized VP7 trimers to dissociate from the virion. This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7. During the virus exit from the host cell, VP4 seems to be required to target the newly formed virions to the host cell lipid rafts.[HAMAP-Rule:MF_04132] Outer capsid protein VP5*: Forms the spike 'foot' and 'body' and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.[HAMAP-Rule:MF_04132] Outer capsid protein VP8*: Forms the head of the spikes and mediates the recognition of specific host cell surface glycans. 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. In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry.[HAMAP-Rule:MF_04132] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4yfw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4yfw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Group a rotaviruses]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hu, L]]
| + | [[Category: Rotavirus A]] |
| - | [[Category: Prasad, B V.V]]
| + | [[Category: Hu L]] |
| - | [[Category: Glycan]]
| + | [[Category: Prasad BVV]] |
| - | [[Category: Rotavirus]] | + | |
| - | [[Category: Structural biology]] | + | |
| - | [[Category: Viral protein]] | + | |
| Structural highlights
Function
B6RGK2_9VIRU Outer capsid protein VP4: 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. 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. It is subsequently lost, together with VP7, following virus entry into the host cell. Following entry into the host cell, low intracellular or intravesicular Ca(2+) concentration probably causes the calcium-stabilized VP7 trimers to dissociate from the virion. This step is probably necessary for the membrane-disrupting entry step and the release of VP4, which is locked onto the virion by VP7. During the virus exit from the host cell, VP4 seems to be required to target the newly formed virions to the host cell lipid rafts.[HAMAP-Rule:MF_04132] Outer capsid protein VP5*: Forms the spike 'foot' and 'body' and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.[HAMAP-Rule:MF_04132] Outer capsid protein VP8*: Forms the head of the spikes and mediates the recognition of specific host cell surface glycans. 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. In some other strains, VP8* mediates the attachment to histo-blood group antigens (HBGAs) for viral entry.[HAMAP-Rule:MF_04132]
Publication Abstract from PubMed
Strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type II precursor glycans, and to restrict type II glycan binding in the bovine counterpart. Such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.
Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus.,Hu L, Ramani S, Czako R, Sankaran B, Yu Y, Smith DF, Cummings RD, Estes MK, Venkataram Prasad BV Nat Commun. 2015 Sep 30;6:8346. doi: 10.1038/ncomms9346. PMID:26420502[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hu L, Ramani S, Czako R, Sankaran B, Yu Y, Smith DF, Cummings RD, Estes MK, Venkataram Prasad BV. Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus. Nat Commun. 2015 Sep 30;6:8346. doi: 10.1038/ncomms9346. PMID:26420502 doi:http://dx.doi.org/10.1038/ncomms9346
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