9j6d
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of Chikungunya virus infectious particles, 2f block.== | |
| + | <StructureSection load='9j6d' size='340' side='right'caption='[[9j6d]], [[Resolution|resolution]] 3.11Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9j6d]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus Chikungunya virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9J6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9J6D 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]] 3.11Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9j6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9j6d OCA], [https://pdbe.org/9j6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9j6d RCSB], [https://www.ebi.ac.uk/pdbsum/9j6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9j6d ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A7S7YHM2_CHIKV A0A7S7YHM2_CHIKV] Acts as a viroporin that participates in virus glycoprotein processing and transport to the plasma membrane, cell permeabilization and budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[ARBA:ARBA00093317] Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Furin-cleaved E3 remains associated with spike glycoprotein E1 and mediates pH protection of the latter during the transport via the secretory pathway. After virion release from the host cell, the assembly protein E3 is gradually released in the extracellular space.[ARBA:ARBA00037518] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes febrile illness and acute or chronic arthritis. Most therapeutics are still in the pre-clinical stage. In this study, we report the isolation of two neutralizing antibodies, C34 and C37, from a convalescent patient and investigate their mechanisms of action. Both C34 and C37 exhibit high neutralizing activities in vitro and demonstrate protective effects against CHIKV in a female mouse model. Our functional and structural studies reveal a mechanism that inhibits multiple stages of the virus infection cycle. Both antibodies bind with high affinity to an epitope spanning E2, E1, and the connecting beta-strands, facilitating intra- and inter-virion crosslinking. Cryo-EM structures additionally identify a minor patch located beneath the E3 binding site on E2, which is allosterically exposed upon E3 dissociation during virus maturation. Functional and structural data further suggest that binding to the CHIKV receptor, Mxra8, is obstructed due to a clash between the antibodies and the stalk region of Mxra8. Our results highlight the potential of antibody-based therapeutics against CHIKV and elucidate the mechanisms of monoclonal antibody protection. | ||
| - | + | Neutralizing antibodies against Chikungunya virus and structural elucidation of their mechanism of action.,Han X, Ji C, Tian S, Wang F, Cao GP, Li D, Duan X, Tong Z, Qi J, Wang Q, Huang Q, Zhan BD, Gao GF, Yan J Nat Commun. 2025 Nov 3;16(1):9682. doi: 10.1038/s41467-025-64687-2. PMID:41184282<ref>PMID:41184282</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9j6d" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Chikungunya virus]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gao FG]] | ||
| + | [[Category: Han X]] | ||
| + | [[Category: Ji C]] | ||
| + | [[Category: Tian S]] | ||
| + | [[Category: Wang F]] | ||
| + | [[Category: Yan J]] | ||
Current revision
Structure of Chikungunya virus infectious particles, 2f block.
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Categories: Chikungunya virus | Large Structures | Gao FG | Han X | Ji C | Tian S | Wang F | Yan J
