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)

Summary for 5AJA

• Entry DOI: 10.2210/pdb5aja/pdb
• Descriptor: PROTEIN VPRBP, VPX PROTEIN, SAM DOMAIN AND HD DOMAIN-CONTAINING PROTEIN, ... (5 entities in total)
• Functional Keywords: viral protein, siv, accessory protein, retroviral restriction factor, ubiquitylation, proteasomal degradation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: Q9Y4B6
• Total number of polymer chains: 3
• Total formula weight: 65993.56

Authors

Schwefel, D.,Boucherit, V.C.,Christodoulou, E.,Walker, P.A.,Stoye, J.P.,Bishop, K.N.,Taylor, I.A. (deposition date: 2015-02-20, release date: 2015-04-22, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.649 Å)