3vbs: Difference between revisions

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<StructureSection load='3vbs' size='340' side='right'caption='[[3vbs]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='3vbs' size='340' side='right'caption='[[3vbs]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3vbs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_enterovirus_71 Human enterovirus 71]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VBS FirstGlance]. <br>
<table><tr><td colspan='2'>[[3vbs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterovirus_A71 Enterovirus A71]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VBS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SPH:SPHINGOSINE'>SPH</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]] 3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vbf|3vbf]], [[3vbh|3vbh]], [[3vbo|3vbo]], [[3vbr|3vbr]], [[3vbu|3vbu]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SPH:SPHINGOSINE'>SPH</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=3vbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbs OCA], [https://pdbe.org/3vbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vbs RCSB], [https://www.ebi.ac.uk/pdbsum/3vbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbs 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=3vbs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vbs OCA], [https://pdbe.org/3vbs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vbs RCSB], [https://www.ebi.ac.uk/pdbsum/3vbs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vbs ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/B2ZUN0_9ENTO B2ZUN0_9ENTO]] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611Protein 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).[SAAS:SAAS000199_004_042266RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]  
[https://www.uniprot.org/uniprot/B2ZUN0_HE71 B2ZUN0_HE71] Capsid protein VP0: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation. Allows the capsid to remain inactive before the maturation step.[RuleBase:RU364118] Capsid protein VP1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Capsid protein VP1 mainly forms the vertices of the capsid. Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells. This attachment induces virion internalization. Tyrosine kinases are probably involved in the entry process. After binding to its receptor, the capsid undergoes conformational changes. Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized. Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm. After genome has been released, the channel shrinks.[RuleBase:RU364118Capsid protein VP2: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118]  Capsid protein VP3: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome.[RuleBase:RU364118]  Capsid protein VP4: Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm. After genome has been released, the channel shrinks.[RuleBase:RU364118]  Protease 2A: Cysteine protease that cleaves viral polyprotein and specific host proteins.[RuleBase:RU364118]  Protease 3C: cleaves host DDX58/RIG-I and thus contributes to the inhibition of type I interferon production. Cleaves also host PABPC1.[RuleBase:RU364118Protein 2B: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.[RuleBase:RU364118]  Protein 2C: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[RuleBase:RU364118] Protein 3A: Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the dissassembly of the Golgi complex, possibly through GBF1 interaction. This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface.[RuleBase:RU364118]  Protein 3AB: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.[RuleBase:RU364118]  Protein 3CD: Is involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. The 3C domain in the context of protein 3CD may have an RNA binding activity.[RuleBase:RU364118]  RNA-directed RNA polymerase: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[RuleBase:RU364118]  Viral protein genome-linked: acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome. VPg may be removed in the cytoplasm by an unknown enzyme termed "unlinkase". VPg is not cleaved off virion genomes because replicated genomic RNA are encapsidated at the site of replication.[RuleBase:RU364118]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention.
 
A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71.,Wang X, Peng W, Ren J, Hu Z, Xu J, Lou Z, Li X, Yin W, Shen X, Porta C, Walter TS, Evans G, Axford D, Owen R, Rowlands DJ, Wang J, Stuart DI, Fry EE, Rao Z Nat Struct Mol Biol. 2012 Mar 4. doi: 10.1038/nsmb.2255. PMID:22388738<ref>PMID:22388738</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vbs" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human enterovirus 71]]
[[Category: Enterovirus A71]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Axford, D]]
[[Category: Axford D]]
[[Category: Evans, G]]
[[Category: Evans G]]
[[Category: Fry, E E]]
[[Category: Fry EE]]
[[Category: Hu, Z]]
[[Category: Hu Z]]
[[Category: Li, X]]
[[Category: Li X]]
[[Category: Lou, Z]]
[[Category: Lou Z]]
[[Category: Owen, R]]
[[Category: Owen R]]
[[Category: Peng, W]]
[[Category: Peng W]]
[[Category: Porta, C]]
[[Category: Porta C]]
[[Category: Rao, Z]]
[[Category: Rao Z]]
[[Category: Ren, J]]
[[Category: Ren J]]
[[Category: Rowlands, D J]]
[[Category: Rowlands DJ]]
[[Category: Shen, X]]
[[Category: Shen X]]
[[Category: Stuart, D I]]
[[Category: Stuart DI]]
[[Category: Walter, T S]]
[[Category: Walter TS]]
[[Category: Wang, J]]
[[Category: Wang J]]
[[Category: Wang, X]]
[[Category: Wang X]]
[[Category: Xu, J]]
[[Category: Xu J]]
[[Category: Yin, W]]
[[Category: Yin W]]
[[Category: Adaptor-sensor]]
[[Category: Enterovirus uncoating]]
[[Category: Hand-foot-and-mouth disease]]
[[Category: Icosahedral virus]]
[[Category: Pocket factor]]
[[Category: Virus]]

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