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

Abstract

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.

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Figure 1: a, Sequence and domain structure of HHR23A.
Figure 2: Abrogation of alleviation of Vpr-induced cell cycle arrest by overexpression of a 134-residue C-terminal portion of HHR23A, HHR23A(B213trunc), that contains a deletion of the C-terminal UBA domain.
Figure 3: a, 300 ms 2D WATERGATE-NOESY spectrum of the HHR23A UBA domain 2.
Figure 4: a, Stereo view of the final set of 10 structures.

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Acknowledgements

AcknowledgmentThis work was supported by NIH grants to J.F., I.S.Y.C. and E.S.W.-W.

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Correspondence to Juli Feigon.

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Dieckmann, T., Withers-Ward, E., Jarosinski, M. et al. Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr. Nat Struct Mol Biol 5, 1042–1047 (1998). https://doi.org/10.1038/4220

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