4j4j | pdb_00004j4j

Crystal structure of the APOBEC3F Vif binding domain

spinqualitylabelsall models 4j4j, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4j4j is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Gene: APOBEC3F (HUMAN) Activity: Cytidine deaminase, with EC number 3.5.4.5 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The human APOBEC3 family of DNA cytosine deaminases serves as a front-line intrinsic immune response to inhibit the replication of diverse retroviruses. APOBEC3F and APOBEC3G are the most potent factors against HIV-1. As a countermeasure, HIV-1 viral infectivity factor (Vif) targets APOBEC3s for proteasomal degradation. Here we report the crystal structure of the Vif-binding domain in APOBEC3F and a novel assay to assess Vif-APOBEC3 binding. Our results point to an amphipathic surface that is conserved in APOBEC3s as critical for Vif susceptibility in APOBEC3F. Electrostatic interactions likely mediate Vif binding. Moreover, structure-guided mutagenesis reveals a straight ssDNA-binding groove distinct from the Vif-binding site, and an 'aromatic switch' is proposed to explain DNA substrate specificities across the APOBEC3 family. This study opens new lines of inquiry that will further our understanding of APOBEC3-mediated retroviral restriction and provides an accurate template for structure-guided development of inhibitors targeting the APOBEC3-Vif axis. Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F.,Siu KK, Sultana A, Azimi FC, Lee JE Nat Commun. 2013 Nov 4;4:2593. doi: 10.1038/ncomms3593. PMID:24185281 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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