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PDBsum entry 2jf5
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protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
2jf5

 

 

 

 

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Contents
Protein chains
75 a.a. *
Ligands
_CD ×2
Metals
_MG
_CO ×2
_CL
Waters ×78
* Residue conservation analysis
PDB id:
2jf5
Name: Signaling protein
Title: Crystal structure of lys63-linked di-ubiquitin
Structure: Ubiquitin. Chain: a, b. Synonym: di-ubiquitin, lys63-linked. Engineered: yes. Other_details: iso-peptide link between a-lys63 and b-gly76
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.95Å     R-factor:   0.208     R-free:   0.250
Authors: D.Komander,P.Odenwaelder,D.Barford
Key ref: D.Komander et al. (2009). Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. Embo Rep, 10, 466-473. PubMed id: 19373254
Date:
26-Jan-07     Release date:   05-Feb-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
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

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Embo Rep 10:466-473 (2009)
PubMed id: 19373254  
 
 
Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains.
D.Komander, F.Reyes-Turcu, J.D.Licchesi, P.Odenwaelder, K.D.Wilkinson, D.Barford.
 
  ABSTRACT  
 
At least eight types of ubiquitin chain exist, and individual linkages affect distinct cellular processes. The only distinguishing feature of differently linked ubiquitin chains is their structure, as polymers of the same unit are chemically identical. Here, we have crystallized Lys 63-linked and linear ubiquitin dimers, revealing that both adopt equivalent open conformations, forming no contacts between ubiquitin molecules and thereby differing significantly from Lys 48-linked ubiquitin chains. We also examined the specificity of various deubiquitinases (DUBs) and ubiquitin-binding domains (UBDs). All analysed DUBs, except CYLD, cleave linear chains less efficiently compared with other chain types, or not at all. Likewise, UBDs can show chain specificity, and are able to select distinct linkages from a ubiquitin chain mixture. We found that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO (NF-kappaB essential modifier) binds to linear chains exclusively, whereas the NZF (Npl4 zinc finger) domain of TAB2 (TAK1 binding protein 2) is Lys 63 specific. Our results highlight remarkable specificity determinants within the ubiquitin system.
 

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
22334143 L.Davis, and J.W.Chin (2012).
Designer proteins: applications of genetic code expansion in cell biology.
  Nat Rev Mol Cell Biol, 13, 168-182.  
22266820 L.Feng, and J.Chen (2012).
The E3 ligase RNF8 regulates KU80 removal and NHEJ repair.
  Nat Struct Mol Biol, 19, 201-206.  
22948927 S.S.Cha, Y.J.An, C.S.Jeong, M.K.Kim, S.G.Lee, K.H.Lee, and B.H.Oh (2012).
Experimental phasing using zinc anomalous scattering.
  Acta Crystallogr D Biol Crystallogr, 68, 1253-1258.
PDB codes: 4dt3 4dwz 4fc5
22820888 Y.Kulathu, and D.Komander (2012).
Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages.
  Nat Rev Mol Cell Biol, 13, 508-523.  
23201676 Y.Ye, G.Blaser, M.H.Horrocks, M.J.Ruedas-Rama, S.Ibrahim, A.A.Zhukov, A.Orte, D.Klenerman, S.E.Jackson, and D.Komander (2012).
Ubiquitin chain conformation regulates recognition and activity of interacting proteins.
  Nature, 492, 266-270.  
21131906 A.E.Johnson, and K.L.Gould (2011).
Dma1 ubiquitinates the SIN scaffold, Sid4, to impede the mitotic localization of Plo1 kinase.
  EMBO J, 30, 341-354.  
21455173 B.Gerlach, S.M.Cordier, A.C.Schmukle, C.H.Emmerich, E.Rieser, T.L.Haas, A.I.Webb, J.A.Rickard, H.Anderton, W.W.Wong, U.Nachbur, L.Gangoda, U.Warnken, A.W.Purcell, J.Silke, and H.Walczak (2011).
Linear ubiquitination prevents inflammation and regulates immune signalling.
  Nature, 471, 591-596.  
21540891 C.Behrends, and J.W.Harper (2011).
Constructing and decoding unconventional ubiquitin chains.
  Nat Struct Mol Biol, 18, 520-528.  
21448225 C.Grabbe, K.Husnjak, and I.Dikic (2011).
The spatial and temporal organization of ubiquitin networks.
  Nat Rev Mol Cell Biol, 12, 295-307.  
21092369 D.Barford (2011).
Structure, function and mechanism of the anaphase promoting complex (APC/C).
  Q Rev Biophys, 44, 153-190.  
21119682 E.W.Harhaj, and V.M.Dixit (2011).
Deubiquitinases in the regulation of NF-κB signaling.
  Cell Res, 21, 22-39.  
21332354 J.H.Hurley, and H.Stenmark (2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
  Annu Rev Biophys, 40, 119-142.  
21448133 J.Staal, Y.Driege, T.Bekaert, A.Demeyer, D.Muyllaert, P.Van Damme, K.Gevaert, and R.Beyaert (2011).
T-cell receptor-induced JNK activation requires proteolytic inactivation of CYLD by MALT1.
  EMBO J, 30, 1742-1752.  
21151032 L.Bedford, J.Lowe, L.R.Dick, R.J.Mayer, and J.E.Brownell (2011).
Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets.
  Nat Rev Drug Discov, 10, 29-46.  
21266548 M.Akutsu, Y.Ye, S.Virdee, J.W.Chin, and D.Komander (2011).
Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains.
  Proc Natl Acad Sci U S A, 108, 2228-2233.
PDB codes: 3phu 3phw 3phx
21468303 R.Ernst, J.H.Claessen, B.Mueller, S.Sanyal, E.Spooner, A.G.van der Veen, O.Kirak, C.D.Schlieker, W.A.Weihofen, and H.L.Ploegh (2011).
Enzymatic blockade of the ubiquitin-proteasome pathway.
  PLoS Biol, 8, e1000605.  
21345146 R.Massoumi (2011).
CYLD: a deubiquitination enzyme with multiple roles in cancer.
  Future Oncol, 7, 285-297.  
21135874 T.Gantke, S.Sriskantharajah, and S.C.Ley (2011).
Regulation and function of TPL-2, an IκB kinase-regulated MAP kinase kinase kinase.
  Cell Res, 21, 131-145.  
21278740 T.Inobe, S.Fishbain, S.Prakash, and A.Matouschek (2011).
Defining the geometry of the two-component proteasome degron.
  Nat Chem Biol, 7, 161-167.  
20622874 A.Bremm, S.M.Freund, and D.Komander (2010).
Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne.
  Nat Struct Mol Biol, 17, 939-947.
PDB code: 2xew
20923877 D.Boehm, B.E.Gewurz, E.Kieff, and E.Cahir-McFarland (2010).
Epstein-Barr latent membrane protein 1 transformation site 2 activates NF-kappaB in the absence of NF-kappaB essential modifier residues 133-224 or 373-419.
  Proc Natl Acad Sci U S A, 107, 18103-18108.  
19853612 D.Fushman, and O.Walker (2010).
Exploring the linkage dependence of polyubiquitin conformations using molecular modeling.
  J Mol Biol, 395, 803-814.  
20181483 F.Liu, and K.J.Walters (2010).
Multitasking with ubiquitin through multivalent interactions.
  Trends Biochem Sci, 35, 352-360.  
20351172 F.Wu-Baer, T.Ludwig, and R.Baer (2010).
The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function.
  Mol Cell Biol, 30, 2787-2798.  
20010814 H.Ashida, M.Kim, M.Schmidt-Supprian, A.Ma, M.Ogawa, and C.Sasakawa (2010).
A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response.
  Nat Cell Biol, 12, 66.  
20551964 H.D.Ulrich, and H.Walden (2010).
Ubiquitin signalling in DNA replication and repair.
  Nat Rev Mol Cell Biol, 11, 479-489.  
  21113390 H.Habelhah (2010).
Emerging complexity of protein ubiquitination in the NF-κB pathway.
  Genes Cancer, 1, 735-747.  
  20357899 H.Wu, Y.C.Lo, and S.C.Lin (2010).
Recent advances in polyubiquitin chain recognition.
  F1000 Biol Rep, 2, 1-5.  
  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.  
20442859 J.G.Magadán, F.J.Pérez-Victoria, R.Sougrat, Y.Ye, K.Strebel, and J.S.Bonifacino (2010).
Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps.
  PLoS Pathog, 6, e1000869.  
21124883 J.Moretti, P.Chastagner, S.Gastaldello, S.F.Heuss, A.M.Dirac, R.Bernards, M.G.Masucci, A.Israël, and C.Brou (2010).
The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation.
  PLoS Biol, 8, e1000545.  
19772915 L.M.Kingeter, and B.C.Schaefer (2010).
Malt1 and cIAP2-Malt1 as effectors of NF-kappaB activation: kissing cousins or distant relatives?
  Cell Signal, 22, 9.  
20154702 M.J.Bertrand, and P.Vandenabeele (2010).
RIP1's function in NF-kappaB activation: from master actor to onlooker.
  Cell Death Differ, 17, 379-380.  
19955178 P.Broglie, K.Matsumoto, S.Akira, D.L.Brautigan, and J.Ninomiya-Tsuji (2010).
Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway.
  J Biol Chem, 285, 2333-2339.  
20029837 S.M.Jeram, T.Srikumar, X.D.Zhang, H.Anne Eisenhauer, R.Rogers, P.G.Pedrioli, M.Matunis, and B.Raught (2010).
An improved SUMmOn-based methodology for the identification of ubiquitin and ubiquitin-like protein conjugation sites identifies novel ubiquitin-like protein chain linkages.
  Proteomics, 10, 254-265.  
20802491 S.Virdee, Y.Ye, D.P.Nguyen, D.Komander, and J.W.Chin (2010).
Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase.
  Nat Chem Biol, 6, 750-757.
PDB code: 2xk5
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.  
20030582 V.Nagy, and I.Dikic (2010).
Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity.
  Biol Chem, 391, 163-169.  
19858201 A.D.Jacobson, N.Y.Zhang, P.Xu, K.J.Han, S.Noone, J.Peng, and C.W.Liu (2009).
The lysine 48 and lysine 63 ubiquitin conjugates are processed differently by the 26 s proteasome.
  J Biol Chem, 284, 35485-35494.  
19626045 D.Komander, M.J.Clague, and S.Urbé (2009).
Breaking the chains: structure and function of the deubiquitinases.
  Nat Rev Mol Cell Biol, 10, 550-563.  
19422324 F.J.Ivins, M.G.Montgomery, S.J.Smith, A.C.Morris-Davies, I.A.Taylor, and K.Rittinger (2009).
NEMO oligomerization and its ubiquitin-binding properties.
  Biochem J, 421, 243-251.  
19909372 H.Shinohara, and T.Kurosaki (2009).
Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling.
  Immunol Rev, 232, 300-318.  
20003470 I.A.Qureshi, F.Ferron, C.C.Seh, P.Cheung, and J.Lescar (2009).
Crystallographic structure of ubiquitin in complex with cadmium ions.
  BMC Res Notes, 2, 251.
PDB code: 3h1u
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.  
19956206 I.Dikic, and V.Dötsch (2009).
Ubiquitin linkages make a difference.
  Nat Struct Mol Biol, 16, 1209-1210.  
19543231 K.Iwai, and F.Tokunaga (2009).
Linear polyubiquitination: a new regulator of NF-kappaB activation.
  EMBO Rep, 10, 706-713.  
19731378 S.D.Weeks, K.C.Grasty, L.Hernandez-Cuebas, and P.J.Loll (2009).
Crystal structures of Lys-63-linked tri- and di-ubiquitin reveal a highly extended chain architecture.
  Proteins, 77, 753-759.
PDB codes: 3h7p 3h7s
19948475 T.E.Messick, and R.A.Greenberg (2009).
The ubiquitin landscape at DNA double-strand breaks.
  J Cell Biol, 187, 319-326.  
19935683 Y.Kulathu, M.Akutsu, A.Bremm, K.Hofmann, and D.Komander (2009).
Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.
  Nat Struct Mol Biol, 16, 1328-1330.
PDB codes: 2wwz 2wx0 2wx1
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
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 code is shown on the right.

 

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