Dieckmann T, Withers-Ward E S, Jarosinski M A, Liu C F, Chen I S, Feigon J
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California at Los Angeles, 90095, USA.
Nat Struct Biol. 1998 Dec;5(12):1042-7. doi: 10.1038/4220.
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 subsequent apoptosis. It has been shown to interact specifically with the second UBA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. The three dimensional structure of the UBA domain, determined by NMR spectroscopy, is presented. The protein domain forms a compact three-helix bundle. One side of the protein has a hydrophobic surface that is the most likely Vpr target site.
HIV-1蛋白Vpr对多种病毒功能至关重要，包括其在G2/M检查点阻滞T细胞并诱导随后凋亡的独特能力。已证明它能与DNA修复蛋白HHR23A中发现的第二个UBA（泛素相关）结构域特异性相互作用，HHR23A是一种高度进化保守的蛋白。该结构域是泛素化途径的某些成员、紫外线切除修复蛋白和某些蛋白激酶中常见的序列基序。本文展示了通过核磁共振光谱法确定的UBA结构域的三维结构。该蛋白结构域形成一个紧密的三螺旋束。蛋白的一侧有一个疏水表面，这很可能是Vpr的靶位点。
