Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr

The HIV-1 protein Vpr is critical for a number of viral functions including a unique ability to arrest T-cells at a G2/M checkpoint and induce subsequ ent apoptosis. It has been shown to interact specifically with the second U BA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurrin g sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases, The three dimensional struct ure of the UBA domain, determined by NMR spectroscopy, is presented. The pr otein domain forms a compact three-helix bundle. One side of the protein ha s a hydrophobic surface that is the most likely Vpr target site.