5AJA

Crystal structure of mandrill SAMHD1 (amino acid residues 1-114) bound to Vpx isolated from mandrill and human DCAF1 (amino acid residues 1058-1396)

5AJA の概要

• エントリーDOI: 10.2210/pdb5aja/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: viral protein, siv, accessory protein, retroviral restriction factor, ubiquitylation, proteasomal degradation
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm: Q9Y4B6
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65993.56

構造登録者

Schwefel, D.,Boucherit, V.C.,Christodoulou, E.,Walker, P.A.,Stoye, J.P.,Bishop, K.N.,Taylor, I.A. (登録日: 2015-02-20, 公開日: 2015-04-22, 最終更新日: 2024-01-10)

主引用文献

Schwefel, D.,Boucherit, V.C.,Christodoulou, E.,Walker, P.A.,Stoye, J.P.,Bishop, K.N.,Taylor, I.A.
Molecular Determinants for Recognition of Divergent Samhd1 Proteins by the Lentiviral Accessory Protein Vpx.
Cell Host Microbe., 17:489-, 2015

PubMed Abstract: The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication.

PubMed: 25856754
DOI: 10.1016/J.CHOM.2015.03.004

実験手法

X-RAY DIFFRACTION (2.649 Å)