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Publication Abstract from PubMed

Human APOBEC3 (A3) cytidine deaminases are antiviral factors that are particularly potent against retroviruses. As a countermeasure, HIV-1 uses a viral infectivity factor (Vif) to target specific human A3s for proteasomal degradation. Vif recruits cellular transcription cofactor CBF-beta and Cullin-5 (CUL5) RING E3 ubiquitin ligase to bind different A3s distinctively, but how this is accomplished remains unclear in the absence of the atomic structure of the complex. Here, we present the cryo-EM structures of HIV-1 Vif in complex with human A3H, CBF-beta and components of CUL5 ubiquitin ligase (CUL5, ELOB, and ELOC). Vif nucleates the entire complex by directly binding four human proteins, A3H, CBF-beta, CUL5, and ELOC. The structures reveal a large interface area between A3H and Vif, primarily mediated by an alpha-helical side of A3H and a five-stranded beta-sheet of Vif. This A3H-Vif interface unveils the basis for sensitivity-modulating polymorphism of both proteins, including a previously reported gain-of-function mutation in Vif isolated from HIV/AIDS patients. Our structural and functional results provide insights into the remarkable interplay between HIV and humans and would inform development efforts for anti-HIV therapeutics.

Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.,Ito F, Alvarez-Cabrera AL, Kim K, Zhou ZH, Chen XS Nat Commun. 2023 Aug 28;14(1):5241. doi: 10.1038/s41467-023-40955-x. PMID:37640699^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.