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PDBsum entry 2wx0
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protein metals Protein-protein interface(s) links
Protein binding PDB id
2wx0

 

 

 

 

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Contents
Protein chains
72 a.a. *
31 a.a. *
30 a.a. *
Metals
_ZN ×2
Waters ×103
* Residue conservation analysis
PDB id:
2wx0
Name: Protein binding
Title: Tab2 nzf domain in complex with lys63-linked di-ubiquitin, p21
Structure: Ubiquitin. Chain: a, b, e, f. Engineered: yes. Mitogen-activated protein kinase kinase kinase 7- interacting protein 2. Chain: c, g. Fragment: tab2 nzf domain, residues 663-693. Synonym: tak1-binding protein 2. Engineered: yes
Source: Synthetic: yes. Bos taurus. Organism_taxid: 9913. Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.40Å     R-factor:   0.177     R-free:   0.236
Authors: Y.Kulathu,M.Akutsu,A.Bremm,K.Hofmann,D.Komander
Key ref:
Y.Kulathu et al. (2009). Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain. Nat Struct Biol, 16, 1328-1330. PubMed id: 19935683 DOI: 10.1038/nsmb.1731
Date:
30-Oct-09     Release date:   24-Nov-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0CH28  (UBC_BOVIN) -  Polyubiquitin-C from Bos taurus
Seq:
Struc: 		 
Seq:
Struc: 		690 a.a.
72 a.a.
Protein chain
Pfam   ArchSchema ?
Q9NYJ8  (TAB2_HUMAN) -  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		693 a.a.
31 a.a.
Protein chain
Pfam   ArchSchema ?
Q9NYJ8  (TAB2_HUMAN) -  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		693 a.a.
30 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

 

 
DOI no: 10.1038/nsmb.1731 Nat Struct Biol 16:1328-1330 (2009)
PubMed id: 19935683  
 
 
Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.
Y.Kulathu, M.Akutsu, A.Bremm, K.Hofmann, D.Komander.
 
  ABSTRACT  
 
The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.
 
  Selected figure(s)  
 
Figure 1.
(a) Structure of TAB2 (red, zinc as yellow sphere coordinated by orange cysteine residues) bound to diubiquitin (green, distal Ub; cyan, proximal Ub). Ile44, Val70 and Leu8 are shown as blue sticks. 2|F[0]| – |F[c]| electron density at 1 covers Gly75, Gly76 and Lys63. (b) Selected residues of TAB2 interacting with ubiquitin are shown in orange. Dotted lines indicate hydrogen bonds. (c) Arrangement of diubiquitin complexes in the crystallographic lattice; two asymmetric units are shown. A dotted line indicates where the continuous chain can form. A schematic illustrates how the triubiquitin complex is arranged in the crystal lattice. 		Figure 3.
(a) Binding of TAB2 NZF to Lys63-linked and linear (Lin) di- and tetraubiquitin. (b) Close-up of the Lys63 linkage showing the position of Met1 at 10.8 Å distance. (c) Binding of TAB2 NZF to Lys63- and Lys48-linked di- and tetraubiquitin. (d) Comparison of TAB2–Lys63-diubiquitin and hHR23A UBA2–Lys48-diubiquitin (PDB 1ZO6 (ref. 8)). (e) Superposition of the distal ubiquitin moieties (dark green) from d, with TAB2 shown. Because of the flexible isopeptide linker, the proximal ubiquitin of Lys48-diubiquitin (light green) can rotate to adopt a similar conformation as Lys63-diubiquitin on TAB2 (see also Supplementary Fig. 6).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2009, 16, 1328-1330) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22157957 J.D.Licchesi, J.Mieszczanek, T.E.Mevissen, T.J.Rutherford, M.Akutsu, S.Virdee, F.El Oualid, J.W.Chin, H.Ovaa, M.Bienz, and D.Komander (2012).
An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains.
  Nat Struct Mol Biol, 19, 62-71.
PDB code: 3zrh
21540891 C.Behrends, and J.W.Harper (2011).
Constructing and decoding unconventional ubiquitin chains.
  Nat Struct Mol Biol, 18, 520-528.  
21242292 D.K.Stringer, and R.C.Piper (2011).
A single ubiquitin is sufficient for cargo protein entry into MVBs in the absence of ESCRT ubiquitination.
  J Cell Biol, 192, 229-242.  
21232017 H.Wajant, and P.Scheurich (2011).
TNFR1-induced activation of the classical NF-κB pathway.
  FEBS J, 278, 862-876.  
21332354 J.H.Hurley, and H.Stenmark (2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
  Annu Rev Biophys, 40, 119-142.  
20345847 A.S.Shifera (2010).
The zinc finger domain of IKKγ (NEMO) protein in health and disease.
  J Cell Mol Med, 14, 2404-2414.  
21111228 F.Ikeda, N.Crosetto, and I.Dikic (2010).
What determines the specificity and outcomes of ubiquitin signaling?
  Cell, 143, 677-681.  
20181483 F.Liu, and K.J.Walters (2010).
Multitasking with ubiquitin through multivalent interactions.
  Trends Biochem Sci, 35, 352-360.  
20551964 H.D.Ulrich, and H.Walden (2010).
Ubiquitin signalling in DNA replication and repair.
  Nat Rev Mol Cell Biol, 11, 479-489.  
  20357899 H.Wu, Y.C.Lo, and S.C.Lin (2010).
Recent advances in polyubiquitin chain recognition.
  F1000 Biol Reports, 2, 1-5.  
21095585 I.Bosanac, I.E.Wertz, B.Pan, C.Yu, S.Kusam, C.Lam, L.Phu, Q.Phung, B.Maurer, D.Arnott, D.S.Kirkpatrick, V.M.Dixit, and S.G.Hymowitz (2010).
Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling.
  Mol Cell, 40, 548-557.
PDB codes: 3oj3 3oj4
20541996 J.M.Winget, and T.Mayor (2010).
The diversity of ubiquitin recognition: hot spots and varied specificity.
  Mol Cell, 38, 627-635.  
20383180 S.G.Hymowitz, and I.E.Wertz (2010).
A20: from ubiquitin editing to tumour suppression.
  Nat Rev Cancer, 10, 332-341.  
20385835 S.Zhao, and H.D.Ulrich (2010).
Distinct consequences of posttranslational modification by linear versus K63-linked polyubiquitin chains.
  Proc Natl Acad Sci U S A, 107, 7704-7709.  
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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