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==Poliovirus type 2 (strain MEF-1) virus-like particle in complex with capsid binder compound 17==
<StructureSection load='8ayz' size='340' side='right'caption='[[8ayz]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ayz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_poliovirus_2 Human poliovirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AYZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 1.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHK:4-[[4-[1,3-bis(oxidanylidene)isoindol-2-yl]phenyl]sulfonylamino]benzoic+acid'>FHK</scene>, <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=8ayz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ayz OCA], [https://pdbe.org/8ayz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ayz RCSB], [https://www.ebi.ac.uk/pdbsum/8ayz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ayz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLG_POL2L POLG_POL2L] 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 interaction of five VP1 proteins in the fivefold axes results in a prominent protusion extending to about 25 Angstroms from the capsid shell. The resulting structure appears as a steep plateau encircled by a valley or cleft. This depression also termed canyon is the receptor binding site. The capsid interacts with human PVR at this site to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis in Hela cells and through caveolin-mediated endocytosis in brain microvascular endothelial cells. 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 (By similarity).  VP0 precursor is a component of immature procapsids (By similarity).  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 (By similarity).  Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).  Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).  Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).  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).  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
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== Publication Abstract from PubMed ==
Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.,Bahar MW, Nasta V, Fox H, Sherry L, Grehan K, Porta C, Macadam AJ, Stonehouse NJ, Rowlands DJ, Fry EE, Stuart DI Commun Biol. 2022 Nov 25;5(1):1293. doi: 10.1038/s42003-022-04252-5. PMID:36434067<ref>PMID:36434067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8ayz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human poliovirus 2]]
[[Category: Large Structures]]
[[Category: Bahar MW]]
[[Category: Fry EE]]
[[Category: Stuart DI]]