8B3X

High resolution crystal structure of dimeric SUDV VP40

Summary for 8B3X

• Entry DOI: 10.2210/pdb8b3x/pdb
• Descriptor: Matrix protein VP40 (2 entities in total)
• Functional Keywords: ebola virus, sudv, vp40, matrix protein, dimer, viral protein
• Biological source: Sudan ebolavirus
• Total number of polymer chains: 1
• Total formula weight: 32603.62

Authors

Werner, A.-D.,Norris, M.,Saphire, E.O.,Becker, S. (deposition date: 2022-09-17, release date: 2023-06-21, Last modification date: 2024-11-20)

Primary citation

Werner, A.D.,Schauflinger, M.,Norris, M.J.,Kluver, M.,Trodler, A.,Herwig, A.,Brandstadter, C.,Dillenberger, M.,Klebe, G.,Heine, A.,Saphire, E.O.,Becker, K.,Becker, S.
The C-terminus of Sudan ebolavirus VP40 contains a functionally important CX n C motif, a target for redox modifications.
Structure, 31:1038-, 2023

PubMed Abstract: The 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.

PubMed: 37392738
DOI: 10.1016/j.str.2023.06.004

Experimental method

X-RAY DIFFRACTION (1.531 Å)