4Z8L

Crystal structure of DCAF1/SIV-MND VPX/MND SAMHD1 NTD ternary complex

4Z8L の概要

• エントリーDOI: 10.2210/pdb4z8l/pdb
• 分子名称: Protein VPRBP, Vpx protein, SAM domain and HD domain-containing protein, ... (5 entities in total)
• 機能のキーワード: hiv, antiviral defense, viral protein-vpx-binding protein complex, viral protein/vpx-binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 130491.18

構造登録者

Koharudin, L.M.,Wu, Y.,Calero, G.,Ahn, J.,Gronenborn, A.M. (登録日: 2015-04-09, 公開日: 2015-06-17, 最終更新日: 2023-09-27)

主引用文献

Wu, Y.,Koharudin, L.M.,Mehrens, J.,DeLucia, M.,Byeon, C.H.,Byeon, I.J.,Calero, G.,Ahn, J.,Gronenborn, A.M.
Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile alpha Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors.
J.Biol.Chem., 290:17935-17945, 2015

PubMed Abstract: Sterile α motif (SAM) and histidine/aspartate (HD)-containing protein 1 (SAMHD1) restricts human/simian immunodeficiency virus infection in certain cell types and is counteracted by the virulence factor Vpx. Current evidence indicates that Vpx recruits SAMHD1 to the Cullin4-Ring Finger E3 ubiquitin ligase (CRL4) by facilitating an interaction between SAMHD1 and the substrate receptor DDB1- and Cullin4-associated factor 1 (DCAF1), thereby targeting SAMHD1 for proteasome-dependent down-regulation. Host-pathogen co-evolution and positive selection at the interfaces of host-pathogen complexes are associated with sequence divergence and varying functional consequences. Two alternative interaction interfaces are used by SAMHD1 and Vpx: the SAMHD1 N-terminal tail and the adjacent SAM domain or the C-terminal tail proceeding the HD domain are targeted by different Vpx variants in a unique fashion. In contrast, the C-terminal WD40 domain of DCAF1 interfaces similarly with the two above complexes. Comprehensive biochemical and structural biology approaches permitted us to delineate details of clade-specific recognition of SAMHD1 by lentiviral Vpx proteins. We show that not only the SAM domain but also the N-terminal tail engages in the DCAF1-Vpx interaction. Furthermore, we show that changing the single Ser-52 in human SAMHD1 to Phe, the residue found in SAMHD1 of Red-capped monkey and Mandrill, allows it to be recognized by Vpx proteins of simian viruses infecting those primate species, which normally does not target wild type human SAMHD1 for degradation.

PubMed: 26045556
DOI: 10.1074/jbc.M115.665513

実験手法

X-RAY DIFFRACTION (2.6 Å)