8AYX
Poliovirus type 3 (strain Saukett) stabilised virus-like particle (PV3 SC8) in complex with GSH and GPP3
Summary for 8AYX
| Entry DOI | 10.2210/pdb8ayx/pdb |
| Related | 8AYY 8AYZ |
| EMDB information | 15725 15726 15727 |
| Descriptor | Capsid protein, VP1, Capsid protein, VP0, Capsid protein, VP3, ... (5 entities in total) |
| Functional Keywords | capsid protein, virus like particle, glutathione, inhibitor, complex |
| Biological source | Human poliovirus 3 More |
| Total number of polymer chains | 3 |
| Total formula weight | 98218.74 |
| Authors | Bahar, M.W.,Fry, E.E.,Stuart, D.I. (deposition date: 2022-09-04, release date: 2022-12-07, Last modification date: 2024-07-24) |
| Primary citation | Bahar, M.W.,Nasta, V.,Fox, H.,Sherry, L.,Grehan, K.,Porta, C.,Macadam, A.J.,Stonehouse, N.J.,Rowlands, D.J.,Fry, E.E.,Stuart, D.I. A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation. Commun Biol, 5:1293-1293, 2022 Cited by PubMed Abstract: 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. PubMed: 36434067DOI: 10.1038/s42003-022-04252-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.5 Å) |
Structure validation
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