5JK7

The X-ray structure of the DDB1-DCAF1-Vpr-UNG2 complex

Summary for 5JK7

• Entry DOI: 10.2210/pdb5jk7/pdb
• Descriptor: DNA damage-binding protein 1, Protein VPRBP, Uracil-DNA glycosylase, ... (4 entities in total)
• Functional Keywords: cullin4-ring e3 ubiquitin ligase hiv-1 vpr ung2, dna binding protein-hydrolase complex, viral protein-dna binding protein complex, viral protein/dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 410111.08

Authors

Calero, G.,Ahn, J.,Wu, Y. (deposition date: 2016-04-26, release date: 2016-10-05, Last modification date: 2024-03-06)

Primary citation

Wu, Y.,Zhou, X.,Barnes, C.O.,DeLucia, M.,Cohen, A.E.,Gronenborn, A.M.,Ahn, J.,Calero, G.
The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction.
Nat.Struct.Mol.Biol., 23:933-940, 2016

PubMed Abstract: The HIV-1 accessory protein Vpr is required for efficient viral infection of macrophages and promotion of viral replication in T cells. Vpr's biological activities are closely linked to the interaction with human DCAF1, a cellular substrate receptor of the Cullin4-RING E3 ubiquitin ligase (CRL4) of the host ubiquitin-proteasome-mediated protein degradation pathway. The molecular details of how Vpr usurps the protein degradation pathway have not been delineated. Here we present the crystal structure of the DDB1-DCAF1-HIV-1-Vpr-uracil-DNA glycosylase (UNG2) complex. The structure reveals how Vpr engages with DCAF1, creating a binding interface for UNG2 recruitment in a manner distinct from the recruitment of SAMHD1 by Vpx proteins. Vpr and Vpx use similar N-terminal and helical regions to bind the substrate receptor, whereas different regions target the specific cellular substrates. Furthermore, Vpr uses molecular mimicry of DNA by a variable loop for specific recruitment of the UNG2 substrate.

PubMed: 27571178
DOI: 10.1038/nsmb.3284

Experimental method

X-RAY DIFFRACTION (3.49 Å)