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PDBsum entry 3a1q

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protein Protein-protein interface(s) links
Gene regulation/signaling protein PDB id
3a1q

 

 

 

 

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Contents
Protein chains
73 a.a. *
76 a.a. *
45 a.a. *
Waters ×156
* Residue conservation analysis
PDB id:
3a1q
Name: Gene regulation/signaling protein
Title: Crystal structure of the mouse rap80 uims in complex with lys63-linked di-ubiquitin
Structure: Ubiquitin. Chain: a, d. Engineered: yes. Mutation: yes. Ubiquitin. Chain: b, e. Engineered: yes. Mutation: yes. Ubiquitin interaction motif-containing protein 1.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: rps27a, uba80, ubcep1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: uimc1, rip110, rxrip110.
Resolution:
2.20Å     R-factor:   0.216     R-free:   0.268
Authors: Y.Sato,A.Yoshikawa,H.Mimura,M.Yamashita,A.Yamagata,S.Fukai
Key ref: Y.Sato et al. (2009). Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80. Embo J, 28, 2461-2468. PubMed id: 19536136
Date:
21-Apr-09     Release date:   21-Jul-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0CG50  (UBC_MOUSE) -  Polyubiquitin-C from Mus musculus
Seq:
Struc:
 
Seq:
Struc:
734 a.a.
73 a.a.
Protein chains
Pfam   ArchSchema ?
P0CG50  (UBC_MOUSE) -  Polyubiquitin-C from Mus musculus
Seq:
Struc:
 
Seq:
Struc:
734 a.a.
76 a.a.*
Protein chains
Pfam   ArchSchema ?
Q5U5Q9  (UIMC1_MOUSE) -  BRCA1-A complex subunit RAP80 from Mus musculus
Seq:
Struc:
 
Seq:
Struc:
727 a.a.
45 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 

 
Embo J 28:2461-2468 (2009)
PubMed id: 19536136  
 
 
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.
Y.Sato, A.Yoshikawa, H.Mimura, M.Yamashita, A.Yamagata, S.Fukai.
 
  ABSTRACT  
 
RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA-damage foci for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs (UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs (RAP80-UIM1-UIM2) in complex with Lys 63-linked di-ubiquitin at 2.2 A resolution. The two UIMs, UIM1 and UIM2, and the alpha-helical inter-UIM region together form a continuous 60 A-long alpha-helix. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties, respectively. Both UIM1 and UIM2 of RAP80 recognize an Ile 44-centered hydrophobic patch on ubiquitin but neither UIM interacts with the Lys 63-linked isopeptide bond. Our structure suggests that the inter-UIM region forms a 12 A-long alpha-helix that ensures that the UIMs are arranged to enable specific binding of Lys 63-linked di-ubiquitin. This was confirmed by pull-down analyses using RAP80-UIM1-UIM2 mutants of various length inter-UIM regions. Further, we show that the Epsin1 tandem UIM, which has an inter-UIM region similar to that of RAP80-UIM1-UIM2, also selectively binds Lys 63-linked di-ubiquitin.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23042607 E.J.Davis, C.Lachaud, P.Appleton, T.J.Macartney, I.Näthke, and J.Rouse (2012).
DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage.
  Nat Struct Mol Biol, 19, 1093-1100.  
22367539 R.Wiener, X.Zhang, T.Wang, and C.Wolberger (2012).
The mechanism of OTUB1-mediated inhibition of ubiquitination.
  Nature, 483, 618-622.
PDB codes: 4dhi 4dhj 4dhz
21332354 J.H.Hurley, and H.Stenmark (2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
  Annu Rev Biophys, 40, 119-142.  
21479981 S.Nakada (2011).
Abnormalities in DNA double-strand break response beyond primary immunodeficiency.
  Int J Hematol, 93, 425-433.  
  21226813 V.Bertelsen, M.M.Sak, K.Breen, M.S.Rødland, L.E.Johannessen, L.M.Traub, E.Stang, and I.H.Madshus (2011).
A chimeric pre-ubiquitinated EGF receptor is constitutively endocytosed in a clathrin-dependent, but kinase-independent manner.
  Traffic, 12, 507-520.  
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
20138522 E.Lauwers, Z.Erpapazoglou, R.Haguenauer-Tsapis, and B.André (2010).
The ubiquitin code of yeast permease trafficking.
  Trends Cell Biol, 20, 196-204.  
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 Rep, 2, 1-5.  
20921134 I.H.Ismail, C.Andrin, D.McDonald, and M.J.Hendzel (2010).
BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair.
  J Cell Biol, 191, 45-60.  
  21113239 J.B.Tang, and R.A.Greenberg (2010).
Connecting the Dots: Interplay Between Ubiquitylation and SUMOylation at DNA Double Strand Breaks.
  Genes Cancer, 1, 787-796.  
20942953 M.Citarelli, S.Teotia, and R.S.Lamb (2010).
Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes.
  BMC Evol Biol, 10, 308.  
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
20383180 S.G.Hymowitz, and I.E.Wertz (2010).
A20: from ubiquitin editing to tumour suppression.
  Nat Rev Cancer, 10, 332-341.  
19763089 E.Laplantine, E.Fontan, J.Chiaravalli, T.Lopez, G.Lakisic, M.Véron, F.Agou, and A.Israël (2009).
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
  EMBO J, 28, 2885-2895.  
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.  
19690555 K.J.Walters, and X.Chen (2009).
Measuring ubiquitin chain linkage: Rap80 uses a molecular ruler mechanism for ubiquitin linkage specificity.
  EMBO J, 28, 2307-2308.  
19696796 L.M.Traub (2009).
Tickets to ride: selecting cargo for clathrin-regulated internalization.
  Nat Rev Mol Cell Biol, 10, 583-596.  
19948475 T.E.Messick, and R.A.Greenberg (2009).
The ubiquitin landscape at DNA double-strand breaks.
  J Cell Biol, 187, 319-326.  
19927120 Y.Sato, A.Yoshikawa, M.Yamashita, A.Yamagata, and S.Fukai (2009).
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3.
  EMBO J, 28, 3903-3909.
PDB codes: 3a9j 3a9k
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 codes are shown on the right.

 

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