8b3x | pdb_00008b3x
High resolution crystal structure of dimeric SUDV VP40
Structural highlights
FunctionVP40_EBOSU Promotes virus assembly and budding by interacting with host proteins of the multivesicular body pathway. May facilitate virus budding by interacting with the nucleocapsid and the plasma membrane. Specific interactions with membrane-associated GP and VP24 during the budding process may also occur. The hexamer form seems to be involved in budding. The octamer form binds RNA, and may play a role in genome replication (By similarity). Publication Abstract from PubMedThe Ebola virus matrix protein VP40 mediates viral budding and negatively regulates viral RNA synthesis. The mechanisms by which these two functions are exerted and regulated are unknown. Using a high-resolution crystal structure of Sudan ebolavirus (SUDV) VP40, we show here that two cysteines in the flexible C-terminal arm of VP40 form a stabilizing disulfide bridge. Notably, the two cysteines are targets of posttranslational redox modifications and interact directly with the host;s thioredoxin system. Mutation of the cysteines impaired the budding function of VP40 and relaxed its inhibitory role for viral RNA synthesis. In line with these results, the growth of recombinant Ebola viruses carrying cysteine mutations was impaired and the released viral particles were elongated. Our results revealed the exact positions of the cysteines in the C-terminal arm of SUDV VP40. The cysteines and/or their redox status are critically involved in the differential regulation of viral budding and viral RNA synthesis. The C-terminus of Sudan ebolavirus VP40 contains a functionally important CX(n)C motif, a target for redox modifications.,Werner AD, Schauflinger M, Norris MJ, Kluver M, Trodler A, Herwig A, Brandstadter C, Dillenberger M, Klebe G, Heine A, Saphire EO, Becker K, Becker S Structure. 2023 Sep 7;31(9):1038-1051.e7. doi: 10.1016/j.str.2023.06.004. Epub , 2023 Jun 30. PMID:37392738[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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