PDBsum entry 1dv0

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protein links
DNA binding protein PDB id
Protein chain
45 a.a. *
* Residue conservation analysis
PDB id:
Name: DNA binding protein
Title: Refined nmr solution structure of thE C-terminal uba domain of the human homologue of rad23a (hhr23a)
Structure: DNA repair protein hhr23a. Chain: a. Fragment: uba domain (c-terminal domain). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 18 models
Authors: E.S.Withers-Ward,T.D.Mueller,I.S.Chen,J.Feigon
Key ref:
E.S.Withers-Ward et al. (2000). Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr. Biochemistry, 39, 14103-14112. PubMed id: 11087358 DOI: 10.1021/bi0017071
19-Jan-00     Release date:   11-Feb-00    
Supersedes: 1uba
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P54725  (RD23A_HUMAN) -  UV excision repair protein RAD23 homolog A
363 a.a.
45 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     nucleotide-excision repair   1 term 


DOI no: 10.1021/bi0017071 Biochemistry 39:14103-14112 (2000)
PubMed id: 11087358  
Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr.
E.S.Withers-Ward, T.D.Mueller, I.S.Chen, J.Feigon.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21304520 C.Heinen, K.Acs, D.Hoogstraten, and N.P.Dantuma (2011).
C-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation.
  Nat Commun, 2, 191.  
20127391 F.Kieken, G.Spagnol, V.Su, A.F.Lau, and P.L.Sorgen (2010).
NMR structure note: UBA domain of CIP75.
  J Biomol NMR, 46, 245-250.
PDB code: 2knz
19401465 M.Hobeika, C.Brockmann, F.Gruessing, D.Neuhaus, G.Divita, M.Stewart, and C.Dargemont (2009).
Structural requirements for the ubiquitin-associated domain of the mRNA export factor Mex67 to bind its specific targets, the transcription elongation THO complex component Hpr1 and nucleoporin FXFG repeats.
  J Biol Chem, 284, 17575-17583.
PDB code: 2khh
18241885 D.Zhang, S.Raasi, and D.Fushman (2008).
Affinity makes the difference: nonselective interaction of the UBA domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin chains.
  J Mol Biol, 377, 162-180.
PDB codes: 2jy5 2jy6
18083707 J.Long, T.R.Gallagher, J.R.Cavey, P.W.Sheppard, S.H.Ralston, R.Layfield, and M.S.Searle (2008).
Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch.
  J Biol Chem, 283, 5427-5440.
PDB codes: 2jy7 2jy8
18184648 Y.Yang, W.Zhang, J.R.Bayrer, and M.A.Weiss (2008).
Doublesex and the regulation of sexual dimorphism in Drosophila melanogaster: structure, function, and mutagenesis of a female-specific domain.
  J Biol Chem, 283, 7280-7292.
PDB codes: 2jz0 2jz1
17486550 A.Verma, S.M.Gopal, J.S.Oh, K.H.Lee, and W.Wenzel (2007).
All-atom de novo protein folding with a scalable evolutionary algorithm.
  J Comput Chem, 28, 2552-2558.  
17635922 G.Kozlov, P.Peschard, B.Zimmerman, T.Lin, T.Moldoveanu, N.Mansur-Azzam, K.Gehring, and M.Park (2007).
Structural basis for UBA-mediated dimerization of c-Cbl ubiquitin ligase.
  J Biol Chem, 282, 27547-27555.
PDB code: 2oo9
17475778 M.Hobeika, C.Brockmann, N.Iglesias, C.Gwizdek, D.Neuhaus, F.Stutz, M.Stewart, G.Divita, and C.Dargemont (2007).
Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67.
  Mol Biol Cell, 18, 2561-2568.
PDB code: 2jp7
17679095 P.Peschard, G.Kozlov, T.Lin, I.A.Mirza, A.M.Berghuis, S.Lipkowitz, M.Park, and K.Gehring (2007).
Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.
  Mol Cell, 27, 474-485.
PDB codes: 2ooa 2oob
16565067 A.Schug, and W.Wenzel (2006).
An evolutionary strategy for all-atom folding of the 60-amino-acid bacterial ribosomal protein l20.
  Biophys J, 90, 4273-4280.  
16421449 E.D.Lowe, N.Hasan, J.F.Trempe, L.Fonso, M.E.Noble, J.A.Endicott, L.N.Johnson, and N.R.Brown (2006).
Structures of the Dsk2 UBL and UBA domains and their complex.
  Acta Crystallogr D Biol Crystallogr, 62, 177-188.
PDB codes: 2bwb 2bwe 2bwf
16731964 Y.G.Chang, A.X.Song, Y.G.Gao, Y.H.Shi, X.J.Lin, X.T.Cao, D.H.Lin, and H.Y.Hu (2006).
Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin.
  Protein Sci, 15, 1248-1259.
PDB codes: 2cwb 2den
16064137 L.Hicke, H.L.Schubert, and C.P.Hill (2005).
Ubiquitin-binding domains.
  Nat Rev Mol Cell Biol, 6, 610-621.  
15780906 R.Farràs, G.Bossis, E.Andermarcher, I.Jariel-Encontre, and M.Piechaczyk (2005).
Mechanisms of delivery of ubiquitylated proteins to the proteasome: new target for anti-cancer therapy?
  Crit Rev Oncol Hematol, 54, 31-51.  
15468324 A.Schug, T.Herges, and W.Wenzel (2004).
All-atom folding of the three-helix HIV accessory protein with an adaptive parallel tempering method.
  Proteins, 57, 792-798.  
14585839 K.Fujiwara, T.Tenno, K.Sugasawa, J.G.Jee, I.Ohki, C.Kojima, H.Tochio, H.Hiroaki, F.Hanaoka, and M.Shirakawa (2004).
Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B.
  J Biol Chem, 279, 4760-4767.
PDB code: 1uel
15322280 M.Kamionka, and J.Feigon (2004).
Structure of the XPC binding domain of hHR23A reveals hydrophobic patches for protein interaction.
  Protein Sci, 13, 2370-2377.
PDB code: 1tp4
15328341 N.Merkley, and G.S.Shaw (2004).
Solution structure of the flexible class II ubiquitin-conjugating enzyme Ubc1 provides insights for polyubiquitin chain assembly.
  J Biol Chem, 279, 47139-47147.
PDB code: 1tte
14707125 T.D.Mueller, M.Kamionka, and J.Feigon (2004).
Specificity of the interaction between ubiquitin-associated domains and ubiquitin.
  J Biol Chem, 279, 11926-11936.  
15142377 T.Kino, and G.N.Pavlakis (2004).
Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1.
  DNA Cell Biol, 23, 193-205.  
15461659 T.Tenno, K.Fujiwara, H.Tochio, K.Iwai, E.H.Morita, H.Hayashi, S.Murata, H.Hiroaki, M.Sato, K.Tanaka, and M.Shirakawa (2004).
Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains.
  Genes Cells, 9, 865-875.  
15029246 X.Yuan, P.Simpson, C.McKeown, H.Kondo, K.Uchiyama, R.Wallis, I.Dreveny, C.Keetch, X.Zhang, C.Robinson, P.Freemont, and S.Matthews (2004).
Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97.
  EMBO J, 23, 1463-1473.
PDB codes: 1v92 1vaz
12857745 B.Ciani, R.Layfield, J.R.Cavey, P.W.Sheppard, and M.S.Searle (2003).
Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone.
  J Biol Chem, 278, 37409-37412.
PDB code: 1q02
12787502 G.Prag, S.Misra, E.A.Jones, R.Ghirlando, B.A.Davies, B.F.Horazdovsky, and J.H.Hurley (2003).
Mechanism of ubiquitin recognition by the CUE domain of Vps9p.
  Cell, 113, 609-620.
PDB codes: 1mn3 1p3q
12972570 M.F.Kleijnen, R.M.Alarcon, and P.M.Howley (2003).
The ubiquitin-associated domain of hPLIC-2 interacts with the proteasome.
  Mol Biol Cell, 14, 3868-3875.  
12970176 T.D.Mueller, and J.Feigon (2003).
Structural determinants for the binding of ubiquitin-like domains to the proteasome.
  EMBO J, 22, 4634-4645.
PDB codes: 1p98 1p9c 1p9d
11875519 R.P.Grant, E.Hurt, D.Neuhaus, and M.Stewart (2002).
Structure of the C-terminal FG-nucleoporin binding domain of Tap/NXF1.
  Nat Struct Biol, 9, 247-251.
PDB code: 1go5
11788722 R.T.Elder, X.Q.Song, M.Chen, K.M.Hopkins, H.B.Lieberman, and Y.Zhao (2002).
Involvement of rhp23, a Schizosaccharomyces pombe homolog of the human HHR23A and Saccharomyces cerevisiae RAD23 nucleotide excision repair genes, in cell cycle control and protein ubiquitination.
  Nucleic Acids Res, 30, 581-591.  
11571271 L.Chen, U.Shinde, T.G.Ortolan, and K.Madura (2001).
Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi-ubiquitin chain assembly.
  EMBO Rep, 2, 933-938.  
11387208 R.Farrás, A.Ferrando, J.Jásik, T.Kleinow, L.Okrész, A.Tiburcio, K.Salchert, C.del Pozo, J.Schell, and C.Koncz (2001).
SKP1-SnRK protein kinase interactions mediate proteasomal binding of a plant SCF ubiquitin ligase.
  EMBO J, 20, 2742-2756.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.