1f4i

SOLUTION STRUCTURE OF THE HHR23A UBA(2) MUTANT P333E, DEFICIENT IN BINDING THE HIV-1 ACCESSORY PROTEIN VPR

spinqualitylabelsall models 1f4i Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1f4i is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RD23A_HUMAN Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize XPC. Involved in vpr-dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 vpr with the host proteasome. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The DNA repair protein HHR23A is a highly conserved protein that functions in nucleotide excision repair. HHR23A contains two ubiquitin associated domains (UBA) that are conserved in a number of proteins with diverse functions involved in ubiquitination, UV excision repair, and signaling pathways via protein kinases. The cellular binding partners of UBA domains remain unclear; however, we previously found that the HHR23A UBA(2) domain interacts specifically with the HIV-1 Vpr protein. Analysis of the low resolution solution structure of HHR23A UBA(2) revealed a hydrophobic loop region of the UBA(2) domain that we predicted was the interface for protein/protein interactions. Here we present results of in vitro binding studies that demonstrate the requirement of this hydrophobic loop region for interaction with human immunodeficiency virus (HIV-1) Vpr. A single point mutation of the Pro at residue 333 to a Glu totally abolishes the binding of HIV-1 Vpr to UBA(2). High resolution NMR structures of the binding deficient UBA(2) mutant P333E as well as of the wild-type UBA(2) domain were determined to compare the effect of this mutation on the structure. Small but significant differences are observed only locally at the site of the mutation. The biochemical and structural analysis confirms the function of the HHR23A UBA(2) GFP-loop as the protein/protein interacting domain. Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr.,Withers-Ward ES, Mueller TD, Chen IS, Feigon J Biochemistry. 2000 Nov 21;39(46):14103-12. PMID:11087358 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UV excision repair protein 3D structures

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