PDBsum entry 1uel

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protein Protein-protein interface(s) links
Gene regulation/protein binding PDB id
Protein chains
95 a.a. *
48 a.a. *
* Residue conservation analysis
PDB id:
Name: Gene regulation/protein binding
Title: Solution structure of ubiquitin-like domain of hhr23b complexed with ubiquitin-interacting motif of proteasome subunit s5a
Structure: Uv excision repair protein rad23 homolog b. Chain: a. Fragment: ubiquitin-like domain (residues 1-95). Synonym: hhr23b. Engineered: yes. 26s proteasome non-atpase regulatory subunit 4. Chain: b. Fragment: ubiquitin-interacting motif (residues 201-248). Synonym: s5a, 26s proteasome regulatory subunit s5a.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: K.Fujiwara,T.Tenno,J.G.Jee,K.Sugasawa,I.Ohki,C.Kojima, H.Tochio,H.Hiroaki,H.Hanaoka,M.Shirakawa,Riken Structural Genomics/proteomics Initiative (Rsgi)
Key ref:
K.Fujiwara et al. (2004). Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B. J Biol Chem, 279, 4760-4767. PubMed id: 14585839 DOI: 10.1074/jbc.M309448200
19-May-03     Release date:   10-Feb-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P54727  (RD23B_HUMAN) -  UV excision repair protein RAD23 homolog B
409 a.a.
95 a.a.*
Protein chain
Pfam   ArchSchema ?
P55036  (PSMD4_HUMAN) -  26S proteasome non-ATPase regulatory subunit 4
377 a.a.
48 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 11 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     proteasome regulatory particle, base subcomplex   1 term 
  Biological process     ubiquitin-dependent protein catabolic process   1 term 


DOI no: 10.1074/jbc.M309448200 J Biol Chem 279:4760-4767 (2004)
PubMed id: 14585839  
Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B.
K.Fujiwara, T.Tenno, K.Sugasawa, J.G.Jee, I.Ohki, C.Kojima, H.Tochio, H.Hiroaki, F.Hanaoka, M.Shirakawa.
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves signaling functions that control several cellular processes. The ubiquitination signal is recognized by downstream effectors, many of which carry a ubiquitin-interacting motif (UIM). Such interactions can be modulated by regulators carrying a ubiquitin-like (UbL) domain, which binds UIM by mimicking ubiquitination. Of them, HR23B regulates the proteasomal targeting of ubiquitinated substrates, DNA repair factors, and other proteins. Here we report the structure of the UIM of the proteasome subunit S5a bound to the UbL domain of HR23B. The UbL domain presents one hydrophobic and two polar contact sites for interaction with UIM. The residues in these contact sites are well conserved in ubiquitin, but ubiquitin also presents a histidine at the interface. The pH-dependent protonation of this residue interferes with the access of ubiquitin to the UIM and the ubiquitin-associated domain (UBA), and its mutation to a smaller residue increases the affinity of ubiquitin for UIM.
  Selected figure(s)  
Figure 1.
FIG. 1. Sequence alignment of UbL and UIM. a, sequences of human HR23B UbL and human ubiquitin. b, sequence alignment of the C-terminal UIM of human proteasome subunit S5a with UIMs of endocytic factors that have been either shown or implied to bind a ubiquitin tag (top panel) and of the N-terminal UIMs of human and S. cerevisiae S5a (Rpn10p) (bottom panel). The sequences are from human (hs), mouse (mm), Drosophila melanogaster (dm), and S. cerevisiae (sc). In a and b, identical residues are highlighted in black, and homologous residues are highlighted in gray. Secondary structural elements of HR23B UbL and S5a UIM are indicated. The residues shown to be important for the complex formation through structural or mutational analyses are marked with asterisks.
Figure 3.
FIG. 3. Structure of the UIM-UbL complex. a, ribbon diagram of the lowest energy structure. UIM and UbL are colored orange and blue, respectively. Secondary structural elements of UbL are indicated. The Tyr48-Ala^49-Gly50 segment of UbL, which forms [T] conformation, is shown in green. b, surface representation of the binding sites of UbL bound to UIM. Hydrophobic and charged residues are shown in yellow and red, respectively, and the [T] segment is shown in green. The side chains of UIM residues that interact with UbL are also shown. c, schematic diagram of the contacts between UIM and UbL. The main chain of UIM is shown in red. The side chains of UIM and UbL residues that form the interface are shown in black and green, respectively. Hydrophobic contacts are indicated by blue dotted lines, and hydrogen bonds and charged interactions are indicated by red dashed lines. Me denotes a methyl group. d, conserved UIM-binding sites in ubiquitin, deduced from the structure of the UIM-UbL complex, are shown on a model of the complex between human ubiquitin and UIM. Hydrophobic and charged residues are colored yellow and red, respectively, on the surface representation of human ubiquitin. The [T] segment, Phe^45-Ala^46-Gly47, is shown in green. His68, which causes the protrusion, is shown in blue. The model was constructed by best fit superposition of the coordinates of human ubiquitin (Protein Data Bank code 1d3z [PDB] ) to those of UbL in the lowest energy structure of the UIM-UbL complex.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 4760-4767) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20949063 A.X.Song, C.J.Zhou, Y.Peng, X.C.Gao, Z.R.Zhou, Q.S.Fu, J.Hong, D.H.Lin, and H.Y.Hu (2010).
Structural transformation of the tandem ubiquitin-interacting motifs in ataxin-3 and their cooperative interactions with ubiquitin chains.
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20053359 N.G.Sgourakis, M.M.Patel, A.E.Garcia, G.I.Makhatadze, and S.A.McCallum (2010).
Conformational dynamics and structural plasticity play critical roles in the ubiquitin recognition of a UIM domain.
  J Mol Biol, 396, 1128-1144.
PDB code: 2kdi
20064467 D.Zhang, T.Chen, I.Ziv, R.Rosenzweig, Y.Matiuhin, V.Bronner, M.H.Glickman, and D.Fushman (2009).
Together, Rpn10 and Dsk2 can serve as a polyubiquitin chain-length sensor.
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19796170 N.Yoshimoto, K.Tatematsu, T.Okajima, K.Tanizawa, and S.Kuroda (2009).
Accumulation of polyubiquitinated proteins by overexpression of RBCC protein interacting with protein kinase C2, a splice variant of ubiquitin ligase RBCC protein interacting with protein kinase C1.
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19423704 Q.S.Fu, C.J.Zhou, H.C.Gao, Y.J.Jiang, Z.R.Zhou, J.Hong, W.M.Yao, A.X.Song, D.H.Lin, and H.Y.Hu (2009).
Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein.
  J Biol Chem, 284, 19043-19052.
PDB codes: 2k89 2k8a 2k8b 2k8c
19111881 S.Fotheringham, M.T.Epping, L.Stimson, O.Khan, V.Wood, F.Pezzella, R.Bernards, and N.B.La Thangue (2009).
Genome-wide loss-of-function screen reveals an important role for the proteasome in HDAC inhibitor-induced apoptosis.
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19468686 V.Su, and A.F.Lau (2009).
Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation.
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19372219 X.Li, G.S.Baillie, and M.D.Houslay (2009).
Mdm2 directs the ubiquitination of beta-arrestin-sequestered cAMP phosphodiesterase-4D5.
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18418689 O.Riess, U.Rüb, A.Pastore, P.Bauer, and L.Schöls (2008).
SCA3: Neurological features, pathogenesis and animal models.
  Cerebellum, 7, 125-137.  
19636891 T.Chen, D.Zhang, Y.Matiuhin, M.Glickman, and D.Fushman (2008).
1H, 13C, and 15N resonance assignment of the ubiquitin-like domain from Dsk2p.
  Biomol NMR Assign, 2, 147-149.  
18083189 Y.C.Kim, and G.Hummer (2008).
Coarse-grained models for simulations of multiprotein complexes: application to ubiquitin binding.
  J Mol Biol, 375, 1416-1433.  
18995839 Y.Matiuhin, D.S.Kirkpatrick, I.Ziv, W.Kim, A.Dakshinamurthy, O.Kleifeld, S.P.Gygi, N.Reis, and M.H.Glickman (2008).
Extraproteasomal Rpn10 restricts access of the polyubiquitin-binding protein Dsk2 to proteasome.
  Mol Cell, 32, 415-425.  
17368669 A.Haririnia, M.D'Onofrio, and D.Fushman (2007).
Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a.
  J Mol Biol, 368, 753-766.  
17242378 B.C.Dickinson, R.Varadan, and D.Fushman (2007).
Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin.
  Protein Sci, 16, 369-378.  
17314036 B.C.O'Connell, and J.W.Harper (2007).
Ubiquitin proteasome system (UPS): what can chromatin do for you?
  Curr Opin Cell Biol, 19, 206-214.  
17351889 E.Tomlinson, N.Palaniyappan, D.Tooth, and R.Layfield (2007).
Methods for the purification of ubiquitinated proteins.
  Proteomics, 7, 1016-1022.  
17646385 J.Hamazaki, K.Sasaki, H.Kawahara, S.Hisanaga, K.Tanaka, and S.Murata (2007).
Rpn10-mediated degradation of ubiquitinated proteins is essential for mouse development.
  Mol Cell Biol, 27, 6629-6638.  
17621610 J.Yan, Y.S.Kim, X.P.Yang, L.P.Li, G.Liao, F.Xia, and A.M.Jetten (2007).
The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair response.
  Cancer Res, 67, 6647-6656.  
17311814 J.Yan, Y.S.Kim, X.P.Yang, M.Albers, M.Koegl, and A.M.Jetten (2007).
Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha.
  Nucleic Acids Res, 35, 1673-1686.  
17319663 Y.E.Ryabov, and D.Fushman (2007).
A model of interdomain mobility in a multidomain protein.
  J Am Chem Soc, 129, 3315-3327.  
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
16907859 E.Jennische, E.Johansson, H.A.Hansson, and I.Jonson (2006).
Immunohistochemical staining patterns using epitope-specific antibodies indicate conformation variants of antisecretory factor/S5a in the CNS.
  APMIS, 114, 529-538.  
16501224 M.C.Tettamanzi, C.Yu, J.S.Bogan, and M.E.Hodsdon (2006).
Solution structure and backbone dynamics of an N-terminal ubiquitin-like domain in the GLUT4-regulating protein, TUG.
  Protein Sci, 15, 498-508.
PDB code: 2al3
16497222 M.J.Hawryluk, P.A.Keyel, S.K.Mishra, S.C.Watkins, J.E.Heuser, and L.M.Traub (2006).
Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein.
  Traffic, 7, 262-281.  
16894394 M.M.Ryan, H.E.Lockstone, S.J.Huffaker, M.T.Wayland, M.J.Webster, and S.Bahn (2006).
Gene expression analysis of bipolar disorder reveals downregulation of the ubiquitin cycle and alterations in synaptic genes.
  Mol Psychiatry, 11, 965-978.  
16462748 S.Hirano, M.Kawasaki, H.Ura, R.Kato, C.Raiborg, H.Stenmark, and S.Wakatsuki (2006).
Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting.
  Nat Struct Mol Biol, 13, 272-277.
PDB code: 2d3g
16609980 Y.Ryabov, and D.Fushman (2006).
Interdomain mobility in di-ubiquitin revealed by NMR.
  Proteins, 63, 787-796.  
15837191 A.Ohno, J.Jee, K.Fujiwara, T.Tenno, N.Goda, H.Tochio, H.Kobayashi, H.Hiroaki, and M.Shirakawa (2005).
Structure of the UBA domain of Dsk2p in complex with ubiquitin molecular determinants for ubiquitin recognition.
  Structure, 13, 521-532.
PDB code: 1wr1
16020535 G.Nicastro, R.P.Menon, L.Masino, P.P.Knowles, N.Q.McDonald, and A.Pastore (2005).
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.
  Proc Natl Acad Sci U S A, 102, 10493-10498.
PDB code: 1yzb
15698469 M.Novatchkova, A.Bachmair, B.Eisenhaber, and F.Eisenhaber (2005).
Proteins with two SUMO-like domains in chromatin-associated complexes: the RENi (Rad60-Esc2-NIP45) family.
  BMC Bioinformatics, 6, 22.  
16252250 R.L.Rich, and D.G.Myszka (2005).
Survey of the year 2004 commercial optical biosensor literature.
  J Mol Recognit, 18, 431-478.  
16056265 S.Elsasser, and D.Finley (2005).
Delivery of ubiquitinated substrates to protein-unfolding machines.
  Nat Cell Biol, 7, 742-749.  
16227581 T.Hara, T.Kamura, S.Kotoshiba, H.Takahashi, K.Fujiwara, I.Onoyama, M.Shirakawa, N.Mizushima, and K.I.Nakayama (2005).
Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle.
  Mol Cell Biol, 25, 9292-9303.  
15265035 M.Albrecht, M.Golatta, U.Wüllner, and T.Lengauer (2004).
Structural and functional analysis of ataxin-2 and ataxin-3.
  Eur J Biochem, 271, 3155-3170.  
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.