9e9v

Structural Insights into HIV-1 Vif-Mediated Ubiquitination and Degradation of APOBEC3H

spinqualitylabelsall models 9e9v, resolution 4.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9e9v is a 13 chain structure with sequence from Escherichia coli BL21(DE3), Homo sapiens, Human immunodeficiency virus 1 and Pan troglodytes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B7T0U6_PANTR Publication Abstract from PubMed The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ligase complex to promote APOBEC3 degradation. Here we resolve key aspects of this counter-defense mechanism by determining a 3.6 A cryo-EM structure of chimpanzee APOBEC3H (cpzA3H) in complex with HIV-1 Vif and three components of the CUL5 E3 ligase-CBFbeta, EloB, and EloC (VCBC). The structure captures cpzA3H as an RNA-mediated dimer within the cpzA3H-VCBC complex, allowing us to examine the role of dimerization. We find that ubiquitination occurs specifically at two lysine residues on the Vif-proximal protomer, while the distal protomer remains unmodified. The structural model of the active cpzA3H-Vif-CUL5 E3 ligase holoenzyme reveals spatial preferences for ubiquitin transfer to the targeted lysine residues. These findings enhance our understanding of A3H degradation and suggest new antiviral strategies targeting this host-virus interface. HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation.,Skorupka KA, Matsuoka K, Hassan B, Ghirlando R, Balachandran V, Chen TH, Walters KJ, Schiffer CA, Wolf M, Iwatani Y, Matsuo H Nat Commun. 2025 Jul 1;16(1):5879. doi: 10.1038/s41467-025-60984-y. PMID:40593686 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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