6NIL

cryoEM structure of the truncated HIV-1 Vif/CBFbeta/A3F complex

Summary for 6NIL

• Entry DOI: 10.2210/pdb6nil/pdb
• EMDB information: 9380
• Descriptor: DNA dC->dU-editing enzyme APOBEC-3F, Core-binding factor subunit beta, Virion infectivity factor, ... (4 entities in total)
• Functional Keywords: human antiviral restriction factor, hiv viral protein, antiviral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 236343.30

Authors

Hu, Y.,Xiong, Y. (deposition date: 2018-12-29, release date: 2019-12-11, Last modification date: 2024-03-20)

Primary citation

Hu, Y.,Desimmie, B.A.,Nguyen, H.C.,Ziegler, S.J.,Cheng, T.C.,Chen, J.,Wang, J.,Wang, H.,Zhang, K.,Pathak, V.K.,Xiong, Y.
Structural basis of antagonism of human APOBEC3F by HIV-1 Vif.
Nat.Struct.Mol.Biol., 26:1176-1183, 2019

PubMed Abstract: HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 interactions to reinstate the A3-catalyzed suppression of human immunodeficiency virus type 1 (HIV-1) replication is a potential approach for antiviral therapeutics. However, the molecular mechanisms by which Vif recognizes A3 proteins remain elusive. Here we report a cryo-EM structure of the Vif-targeted C-terminal domain of human A3F in complex with HIV-1 Vif and the cellular cofactor core-binding factor beta (CBFβ) at 3.9-Å resolution. The structure shows that Vif and CBFβ form a platform to recruit A3F, revealing a direct A3F-recruiting role of CBFβ beyond Vif stabilization, and captures multiple independent A3F-Vif interfaces. Together with our biochemical and cellular studies, our structural findings establish the molecular determinants that are critical for Vif-mediated neutralization of A3F and provide a comprehensive framework of how HIV-1 Vif hijacks the host protein degradation machinery to counteract viral restriction by A3F.

PubMed: 31792451
DOI: 10.1038/s41594-019-0343-6

Experimental method

ELECTRON MICROSCOPY (3.9 Å)