VprBP

spinqualitylabelsall models Human VprBP residues 1045-1396 (pink) complex with Vpr (cyan), DNA damage-binding protein (green) and uracil-DNA glycosylase (yellow) (PDB code 5jk7) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function VprBP (VPR-binding protein) or DDB1- and CUL4-associated factor 1 or DCAF1 is a HIV-1 WD40 protein is essential for DNA replication and embryonic development. VprBP has intrinsic kinase activity and is capable of phosphorylating histone H2A. Recruitment of VprBP by Vpr is essential for HIV-1 VPR activity of initiating the host cell response cycle arresting its G(2) phase following mitosis. VprBP interacts with merlin which is then recruited to the E3 ligase complex resulting in its polyubiquitination and consequently its proteasome-mediated degradation. Relevance VprBP inhibition could be a strategy for the development of anticancer therapeutics. Structural highlights The interactions between VprBP and Vpr are located in a cleft formed by VprBD canonical WD40 seven-blade β-propeller (Alpha Helices,  Beta Strands ,  Loops , Turns) which is lined by acidic residues on one end and hydrophobic residues at the center (Anionic (-) / Cationic (+); Hydrophobic, Polar). The interactions are formed by hydrogen bonds, Vpr Phe residue buried in VprBP hydrophobic pocket and VprBP Trp binding to residues in Vpr pocket.

3D Structures of VprBP

Updated on 03-April-2024

4pxw – hVprBP residues 1039-1401 (mutant) - human
3wa0 – hVprBP residues 1417-1506 + merlin
4p7i – hVprBP residues 998-1058 + merlin
4z8l, 5aja, 4cc9 – hVprBP residues 1057-1396 + VPX + SAMHD1
5jk7 – hVprBP residues 1045-1396 + Vpr + DNA damage-binding protein + uracil-DNA glycosylase

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Jaime Prilusky