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PDBsum entry 1yx6
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protein Protein-protein interface(s) links
Hydrolase PDB id
1yx6

 

 

 

 

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Contents
Protein chains
112 a.a. *
76 a.a. *
* Residue conservation analysis
PDB id:
1yx6
Name: Hydrolase
Title: Solution structure of s5a uim-2/ubiquitin complex
Structure: 26s proteasome non-atpase regulatory subunit 4. Chain: a. Fragment: polyubiquitin binding region of s5a. Synonym: 26s proteasome regulatory subunit s5a, rpn10, multiubiquitin chain binding protein, antisecretory factor-1, af, asf. Engineered: yes. Ubiquitin. Chain: b. Fragment: sequence database residues 1-76.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: psmd4, mcb1. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
NMR struc: 18 models
Authors: Q.Wang,P.Young,K.J.Walters
Key ref:
Q.Wang et al. (2005). Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition. J Mol Biol, 348, 727-739. PubMed id: 15826667 DOI: 10.1016/j.jmb.2005.03.007
Date:
19-Feb-05     Release date:   19-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P55036  (PSMD4_HUMAN) -  26S proteasome non-ATPase regulatory subunit 4 from Homo sapiens
Seq:
Struc: 		377 a.a.
112 a.a.*
Protein chain
Pfam   ArchSchema ?
P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		685 a.a.
76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.jmb.2005.03.007 J Mol Biol 348:727-739 (2005)
PubMed id: 15826667  
 
 
Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition.
Q.Wang, P.Young, K.J.Walters.
 
  ABSTRACT  
 
Ubiquitin is a key regulatory molecule in diverse cellular events. How cells determine the outcome of ubiquitylation remains unclear; however, a likely determinant is the specificity of ubiquitin receptor proteins for polyubiquitin chains of certain length and linkage. Proteasome subunit S5a contains two ubiquitin-interacting motifs (UIMs) through which it recruits ubiquitylated substrates to the proteasome for their degradation. Here, we report the structure of S5a (196-306) alone and complexed with two monoubiquitin molecules. This construct contains the two UIMs of S5a and we reveal their different ubiquitin-binding mechanisms and provide a rationale for their unique specificities for different ubiquitin-like domains. Furthermore, we provide direct evidence that S5a (196-306) binds either K63-linked or K48-linked polyubiquitin, and in both cases prefers longer chains. On the basis of these results we present a model for how S5a and other ubiquitin-binding proteins recognize polyubiquitin.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. S5a (196-306) binds both K48-linked and K63-linked polyubiquitin chains. His-S5a (196-306) on Ni-NTA resin was incubated for two hours with 5 µg of either K48-linked or K63-linked polyubiquitin with a chain length ranging from one to seven (BostonBiochem Inc.). Proteins were fractionated on gels, transferred to a membrane and then probed with a-ubiquitin. Samples of the input polyubiquitin chains used in these experiments are provided on the left. 		Figure 5.
Figure 5. S5a flexible regions allow adaptable binding to tetraubiquitin. In (a) K48-linked tetraubiquitin from a crystal structure (PDB code 1TBE)39 binds each of the UIMs of S5a via its two distal ubiquitin moieties. A snapshot of the two UIMs contacting either (b) neighboring or (c) terminal ubiquitin moieties is provided for K48-linked tetraubiquitin, in which the ubiquitin subunits are not forced to contact each other. The ubiquitin moieties are numbered sequentially according to the position of a hypothetical protein substrate: Ub1 (colored red) would be attached to a protein substrate via its G76. This Figure was generated by using MOLSCRIPT.50
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 348, 727-739) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20541994 A.L.Haas (2010).
Regulating the regulator: Rsp5 ubiquitinates the proteasome.
  Mol Cell, 38, 623-624.  
20440844 A.X.Song, C.J.Zhou, X.Guan, K.H.Sze, and H.Y.Hu (2010).
Solution structure of the N-terminal domain of DC-UbP/UBTD2 and its interaction with ubiquitin.
  Protein Sci, 19, 1104-1109.
PDB code: 2ksn
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.
  PLoS One, 5, e13202.  
20739285 C.Riedinger, J.Boehringer, J.F.Trempe, E.D.Lowe, N.R.Brown, K.Gehring, M.E.Noble, C.Gordon, and J.A.Endicott (2010).
Structure of Rpn10 and its interactions with polyubiquitin chains and the proteasome subunit Rpn12.
  J Biol Chem, 285, 33992-34003.
PDB code: 2x5n
20181483 F.Liu, and K.J.Walters (2010).
Multitasking with ubiquitin through multivalent interactions.
  Trends Biochem Sci, 35, 352-360.  
20399133 H.Fu, Y.L.Lin, and A.S.Fatimababy (2010).
Proteasomal recognition of ubiquitylated substrates.
  Trends Plant Sci, 15, 375-386.  
20541996 J.M.Winget, and T.Mayor (2010).
The diversity of ubiquitin recognition: hot spots and varied specificity.
  Mol Cell, 38, 627-635.  
20525901 K.Ohshima, and K.Igarashi (2010).
Inference for the initial stage of domain shuffling: tracing the evolutionary fate of the PIPSL retrogene in hominoids.
  Mol Biol Evol, 27, 2522-2533.  
20159559 M.G.Bomar, S.D'Souza, M.Bienko, I.Dikic, G.C.Walker, and P.Zhou (2010).
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.
  Mol Cell, 37, 408-417.
PDB code: 2khu
20542005 M.Isasa, E.J.Katz, W.Kim, V.Yugo, S.González, D.S.Kirkpatrick, T.M.Thomson, D.Finley, S.P.Gygi, and B.Crosas (2010).
Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome.
  Mol Cell, 38, 733-745.  
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
21098295 S.Bohn, F.Beck, E.Sakata, T.Walzthoeni, M.Beck, R.Aebersold, F.Förster, W.Baumeister, and S.Nickell (2010).
Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution.
  Proc Natl Acad Sci U S A, 107, 20992-20997.  
19875440 S.S.Safadi, and G.S.Shaw (2010).
Differential interaction of the E3 ligase parkin with the proteasomal subunit S5a and the endocytic protein Eps15.
  J Biol Chem, 285, 1424-1434.  
20471946 X.Chen, B.H.Lee, D.Finley, and K.J.Walters (2010).
Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2.
  Mol Cell, 38, 404-415.
PDB codes: 2kqz 2kr0
19489727 D.Finley (2009).
Recognition and processing of ubiquitin-protein conjugates by the proteasome.
  Annu Rev Biochem, 78, 477-513.  
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.
  Mol Cell, 36, 1018-1033.  
19362814 F.Striebel, W.Kress, and E.Weber-Ban (2009).
Controlled destruction: AAA+ ATPases in protein degradation from bacteria to eukaryotes.
  Curr Opin Struct Biol, 19, 209-217.  
19387488 H.T.Kim, K.P.Kim, T.Uchiki, S.P.Gygi, and A.L.Goldberg (2009).
S5a promotes protein degradation by blocking synthesis of nondegradable forked ubiquitin chains.
  EMBO J, 28, 1867-1877.  
19773779 I.Dikic, S.Wakatsuki, and K.J.Walters (2009).
Ubiquitin-binding domains - from structures to functions.
  Nat Rev Mol Cell Biol, 10, 659-671.  
19328070 J.J.Sims, and R.E.Cohen (2009).
Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80.
  Mol Cell, 33, 775-783.  
19206148 N.Huber, N.Sakai, T.Eismann, T.Shin, S.Kuboki, J.Blanchard, R.Schuster, M.J.Edwards, H.R.Wong, and A.B.Lentsch (2009).
Age-related decrease in proteasome expression contributes to defective nuclear factor-kappaB activation during hepatic ischemia/reperfusion.
  Hepatology, 49, 1718-1728.  
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.
  FEBS J, 276, 6375-6385.  
19683493 N.Zhang, Q.Wang, A.Ehlinger, L.Randles, J.W.Lary, Y.Kang, A.Haririnia, A.J.Storaska, J.L.Cole, D.Fushman, and K.J.Walters (2009).
Structure of the s5a:k48-linked diubiquitin complex and its interactions with rpn13.
  Mol Cell, 35, 280-290.
PDB codes: 2kde 2kdf
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
19581588 S.Nickell, F.Beck, S.H.Scheres, A.Korinek, F.Förster, K.Lasker, O.Mihalache, N.Sun, I.Nagy, A.Sali, J.M.Plitzko, J.M.Carazo, M.Mann, and W.Baumeister (2009).
Insights into the molecular architecture of the 26S proteasome.
  Proc Natl Acad Sci U S A, 106, 11943-11947.  
19240029 T.Uchiki, H.T.Kim, B.Zhai, S.P.Gygi, J.A.Johnston, J.P.O'Bryan, and A.L.Goldberg (2009).
The Ubiquitin-interacting Motif Protein, S5a, Is Ubiquitinated by All Types of Ubiquitin Ligases by a Mechanism Different from Typical Substrate Recognition.
  J Biol Chem, 284, 12622-12632.  
19372219 X.Li, G.S.Baillie, and M.D.Houslay (2009).
Mdm2 Directs the Ubiquitination of {beta}-Arrestin-sequestered cAMP Phosphodiesterase-4D5.
  J Biol Chem, 284, 16170-16182.  
19536136 Y.Sato, A.Yoshikawa, H.Mimura, M.Yamashita, A.Yamagata, and S.Fukai (2009).
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.
  EMBO J, 28, 2461-2468.
PDB code: 3a1q
19832993 Y.Zhang, S.Lu, S.Zhao, X.Zheng, M.Long, and L.Wei (2009).
Positive selection for the male functionality of a co-retroposed gene in the hominoids.
  BMC Evol Biol, 9, 252.  
18054791 A.Haririnia, R.Verma, N.Purohit, M.Z.Twarog, R.J.Deshaies, D.Bolon, and D.Fushman (2008).
Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins.
  J Mol Biol, 375, 979-996.
PDB code: 2jwz
18497827 P.Schreiner, X.Chen, K.Husnjak, L.Randles, N.Zhang, S.Elsasser, D.Finley, I.Dikic, K.J.Walters, and M.Groll (2008).
Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction.
  Nature, 453, 548-552.
PDB codes: 2r2y 2z59
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.  
17351889 E.Tomlinson, N.Palaniyappan, D.Tooth, and R.Layfield (2007).
Methods for the purification of ubiquitinated proteins.
  Proteomics, 7, 1016-1022.  
18047733 L.Madsen, A.Schulze, M.Seeger, and R.Hartmann-Petersen (2007).
Ubiquitin domain proteins in disease.
  BMC Biochem, 8, S1.  
17304240 M.G.Bomar, M.T.Pai, S.R.Tzeng, S.S.Li, and P.Zhou (2007).
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.
  EMBO Rep, 8, 247-251.
PDB code: 2i5o
17189251 S.Ventadour, M.Jarzaguet, S.S.Wing, C.Chambon, L.Combaret, D.Béchet, D.Attaix, and D.Taillandier (2007).
A new method of purification of proteasome substrates reveals polyubiquitination of 20 S proteasome subunits.
  J Biol Chem, 282, 5302-5309.  
17098253 Y.Kang, N.Zhang, D.M.Koepp, and K.J.Walters (2007).
Ubiquitin receptor proteins hHR23a and hPLIC2 interact.
  J Mol Biol, 365, 1093-1101.  
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.  
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
16056265 S.Elsasser, and D.Finley (2005).
Delivery of ubiquitinated substrates to protein-unfolding machines.
  Nat Cell Biol, 7, 742-749.  
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.

 

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