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PDBsum entry 2jy5

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protein links
Signaling protein PDB id
2jy5
Jmol
Contents
Protein chain
52 a.a. *
* Residue conservation analysis
PDB id:
2jy5
Name: Signaling protein
Title: Nmr structure of ubiquilin 1 uba domain
Structure: Ubiquilin-1. Chain: a. Fragment: uba domain. Synonym: protein linking iap with cytoskeleton 1, plic-1, hplic- 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ubqln1, da41, plic1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: pgex-4t1
NMR struc: 10 models
Authors: D.Zhang,S.Raasi,D.Fushman
Key ref:
D.Zhang et al. (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. PubMed id: 18241885 DOI: 10.1016/j.jmb.2007.12.029
Date:
06-Dec-07     Release date:   18-Mar-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9UMX0  (UBQL1_HUMAN) -  Ubiquilin-1
Seq:
Struc:
 
Seq:
Struc:
589 a.a.
52 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of protein ubiquitination   1 term 

 

 
DOI no: 10.1016/j.jmb.2007.12.029 J Mol Biol 377:162-180 (2008)
PubMed id: 18241885  
 
 
Affinity makes the difference: nonselective interaction of the UBA domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin chains.
D.Zhang, S.Raasi, D.Fushman.
 
  ABSTRACT  
 
Ubiquilin/PLIC proteins belong to the family of UBL-UBA proteins implicated in the regulation of the ubiquitin-dependent proteasomal degradation of cellular proteins. A human presenilin-interacting protein, ubiquilin-1, has been suggested as potential therapeutic target for treating Huntington's disease. Ubiquilin's interactions with mono- and polyubiquitins are mediated by its UBA domain, which is one of the tightest ubiquitin binders among known ubiquitin-binding domains. Here we report the three-dimensional structure of the UBA domain of ubiquilin-1 (UQ1-UBA) free in solution and in complex with ubiquitin. UQ1-UBA forms a compact three-helix bundle structurally similar to other known UBAs, and binds to the hydrophobic patch on ubiquitin with a K(d) of 20 microM. To gain structural insights into UQ1-UBA's interactions with polyubiquitin chains, we have mapped the binding interface between UQ1-UBA and Lys48- and Lys63-linked di-ubiquitins and characterized the strength of UQ1-UBA binding to these chains. Our NMR data show that UQ1-UBA interacts with the individual ubiquitin units in both chains in a mode similar to its interaction with mono-ubiquitin, although with an improved binding affinity for the chains. Our results indicate that, in contrast to UBA2 of hHR23A that has strong binding preference for Lys48-linked chains, UQ1-UBA shows little or no binding selectivity toward a particular chain linkage or between the two ubiquitin moieties in the same chain. The structural data obtained in this study provide insights into the possible structural reasons for the diversity of polyubiquitin chain recognition by UBA domains.
 
  Selected figure(s)  
 
Figure 8.
Fig. 8. Comparison of the structure of (a) UQ1-UBA/monoUb complex derived here with the published structures of monoUb complexes with (b) Dsk2-UBA, (c) Ede1-UBA, and (d) Cue2-CUE1 domains (PDB codes 1WR1, 2G3Q, and 1OTR, respectively). Helices in UBAs are colored green (α1), khaki (α2), and magenta (α3) to guide the eye.
Figure 9.
Fig. 9. Structural models show how UQ1-UBA can bind (a) K63- and (b) K48-linked Ub[2] chains and help rationalize (c and d) the differences in linkage selectivity between UQ1-UBA and hHR23A-UBA2. The structures in (a) and (b) were obtained by superimposition of the UQ1-UBA/Ub complex onto the distal and proximal Ubs of each chain, i.e., assuming that UQ1-UBA interacts with each Ub unit in the same way as with monoUb. The latter is justified by the fact that the CSPs in each Ub in these chains upon UQ1-UBA binding are almost identical with those in monoUb (cf Fig. 2 and Fig. 7). The K63-Ub[2] structure is from Ref. 49, the K48-Ub[2] structure shown in (b) corresponds to a fully open conformation of the chain reported in Refs. [54] and [55]. Comparison of the intermolecular contacts stabilizing the hHR23A-UBA2/K48-Ub[2] complex^30 (c) with those in a hypothetical model of a similar complex for UQ1-UBA (d) shows that the interactions that favor the formation of a 1:1 complex in the former are missing in the latter. The structure model in (d) was obtained by replacing the distal Ub/UBA2 pair in (c) with the Ub/UQ1-UBA structure determined in this study (Fig. 8a); this replacement is justified by the fact that the CSPs observed both in the distal Ub and in the UQ1-UBA are essentially the same as in the monoUb/UQ1-UBA complex. In both structures (c and d), the “canonical” Ub-binding side (loop 1 and helix α3) of the corresponding UBA domain is in contact with the hydrophobic patch on the distal Ub, and only the side chains of residues forming contacts between the UBA and the proximal Ub or the Ub–Ub linker are shown in ball-and-stick representation, colored green (UBA) and cyan (Ub). In all these Ub[2] structures (grey) the distal Ub is on the left, the proximal Ub is on the right. The location of G76 (distal Ub) and the side chain (shown as red stick) of K48 or K63 (proximal Ub) that form the isopeptide bond linking the two Ubs in Ub[2] is indicated. The UBAs bound to the distal and proximal Ubs are colored green and blue, respectively.
 
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2008, 377, 162-180) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21305337 L.Cai, D.S.Kosov, and D.Fushman (2011).
Density functional calculations of backbone (15)N shielding tensors in beta-sheet and turn residues of protein G.
  J Biomol NMR, 50, 19-33.  
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
20399133 H.Fu, Y.L.Lin, and A.S.Fatimababy (2010).
Proteasomal recognition of ubiquitylated substrates.
  Trends Plant Sci, 15, 375-386.  
21070969 N.Pashkova, L.Gakhar, S.C.Winistorfer, L.Yu, S.Ramaswamy, and R.C.Piper (2010).
WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover of F box proteins.
  Mol Cell, 40, 433-443.
PDB code: 3odt
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.  
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.  
19620964 J.J.Sims, A.Haririnia, B.C.Dickinson, D.Fushman, and R.E.Cohen (2009).
Avid interactions underlie the Lys63-linked polyubiquitin binding specificities observed for UBA domains.
  Nat Struct Mol Biol, 16, 883-889.  
19722279 J.Song, J.K.Park, J.J.Lee, Y.S.Choi, K.S.Ryu, J.H.Kim, E.Kim, K.J.Lee, Y.H.Jeon, and E.E.Kim (2009).
Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1.
  Protein Sci, 18, 2265-2276.  
19468686 V.Su, and A.F.Lau (2009).
Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation.
  Cell Mol Life Sci, 66, 2819-2833.  
18827983 D.L.Gay, H.Ramón, and P.M.Oliver (2008).
Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity.
  Immunol Res, 42, 51-64.  
18516089 F.Ikeda, and I.Dikic (2008).
Atypical ubiquitin chains: new molecular signals. 'Protein Modifications: Beyond the Usual Suspects' review series.
  EMBO Rep, 9, 536-542.  
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.  
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.