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PDBsum entry 2o6v
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protein ligands Protein-protein interface(s) links
Signaling protein PDB id
2o6v

 

 

 

 

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Contents
Protein chains
75 a.a. *
76 a.a. *
76 a.a. *
Ligands
SO4 ×4
MES ×2
Waters ×149
* Residue conservation analysis
PDB id:
2o6v
Name: Signaling protein
Title: Crystal structure and solution nmr studies of lys48-linked tetraubiquitin at neutral ph
Structure: Ubiquitin. Chain: a, c, e, g. Engineered: yes. Ubiquitin. Chain: b, f. Engineered: yes. Mutation: yes. Ubiquitin. Chain: d, h.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.222     R-free:   0.262
Authors: M.J.Eddins,C.Wolberger
Key ref:
M.J.Eddins et al. (2007). Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH. J Mol Biol, 367, 204-211. PubMed id: 17240395 DOI: 10.1016/j.jmb.2006.12.065
Date:
08-Dec-06     Release date:   13-Feb-07    
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.
75 a.a.
Protein chains
Pfam   ArchSchema ?
P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		685 a.a.
76 a.a.*
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
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 

 
DOI no: 10.1016/j.jmb.2006.12.065 J Mol Biol 367:204-211 (2007)
PubMed id: 17240395  
 
 
Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH.
M.J.Eddins, R.Varadan, D.Fushman, C.M.Pickart, C.Wolberger.
 
  ABSTRACT  
 
Ubiquitin modification of proteins is used as a signal in many cellular processes. Lysine side-chains can be modified by a single ubiquitin or by a polyubiquitin chain, which is defined by an isopeptide bond between the C terminus of one ubiquitin and a specific lysine in a neighboring ubiquitin. Polyubiquitin conformations that result from different lysine linkages presumably differentiate their roles and ability to bind specific targets and enzymes. However, conflicting results have been obtained regarding the precise conformation of Lys48-linked tetraubiquitin. We report the crystal structure of Lys48-linked tetraubiquitin at near-neutral pH. The two tetraubiquitin complexes in the asymmetric unit show the complete connectivity of the chain and the molecular details of the interactions. This tetraubiquitin conformation is consistent with our NMR data as well as with previous studies of diubiquitin and tetraubiquitin in solution at neutral pH. The structure provides a basis for understanding Lys48-linked polyubiquitin recognition under physiological conditions.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. A new conformation of Lys48-linked tetraubiquitin. The tetraubiquitin coloring from proximal ubiquitin to distal ubiquitin is: yellow–cyan–green–blue (1–2–3–4). Rotating 45° in either direction about the x-axis from the center structure shows the interface of the two diubiquitin subunits (1–2 on the left, 3–4 on the right). Figure 1. A new conformation of Lys48-linked tetraubiquitin. The tetraubiquitin coloring from proximal ubiquitin to distal ubiquitin is: yellow–cyan–green–blue (1–2–3–4). Rotating 45° in either direction about the x-axis from the center structure shows the interface of the two diubiquitin subunits (1–2 on the left, 3–4 on the right).
Figure 6.
Figure 6. The hydrophobic surface stripes on the Lys48-linked tetraubiquitin surface showing the orientation of all the ubiquitin Leu8 side-chains. The tetraubiquitin coloring is the same as for Figure 1, with the proximal ubiquitin 1 yellow, and the distal ubiquitin 4 being blue. The Leu8 side-chains are shown in red with the numbers corresponding to the specific ubiquitin in the chain a particular Leu8 is from. Figure 6. The hydrophobic surface stripes on the Lys48-linked tetraubiquitin surface showing the orientation of all the ubiquitin Leu8 side-chains. The tetraubiquitin coloring is the same as for [3]Figure 1, with the proximal ubiquitin 1 yellow, and the distal ubiquitin 4 being blue. The Leu8 side-chains are shown in red with the numbers corresponding to the specific ubiquitin in the chain a particular Leu8 is from.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 367, 204-211) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22237024 G.C.Lander, E.Estrin, M.E.Matyskiela, C.Bashore, E.Nogales, and A.Martin (2012).
Complete subunit architecture of the proteasome regulatory particle.
  Nature, 482, 186-191.  
22266820 L.Feng, and J.Chen (2012).
The E3 ligase RNF8 regulates KU80 removal and NHEJ repair.
  Nat Struct Mol Biol, 19, 201-206.  
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.  
21540891 C.Behrends, and J.W.Harper (2011).
Constructing and decoding unconventional ubiquitin chains.
  Nat Struct Mol Biol, 18, 520-528.  
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.  
20865150 G.Nicastro, S.V.Todi, E.Karaca, A.M.Bonvin, H.L.Paulson, and A.Pastore (2010).
Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3.
  PLoS One, 5, e12430.  
  20357899 H.Wu, Y.C.Lo, and S.C.Lin (2010).
Recent advances in polyubiquitin chain recognition.
  F1000 Biol Rep, 2, 1-5.  
20541996 J.M.Winget, and T.Mayor (2010).
The diversity of ubiquitin recognition: hot spots and varied specificity.
  Mol Cell, 38, 627-635.  
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
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
19373254 D.Komander, F.Reyes-Turcu, J.D.Licchesi, P.Odenwaelder, K.D.Wilkinson, and D.Barford (2009).
Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains.
  EMBO Rep, 10, 466-473.
PDB codes: 2jf5 2w9n
19243136 F.E.Reyes-Turcu, and K.D.Wilkinson (2009).
Polyubiquitin binding and disassembly by deubiquitinating enzymes.
  Chem Rev, 109, 1495-1508.  
19489724 F.E.Reyes-Turcu, K.H.Ventii, and K.D.Wilkinson (2009).
Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.
  Annu Rev Biochem, 78, 363-397.  
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
19047059 M.W.Popp, K.Artavanis-Tsakonas, and H.L.Ploegh (2009).
Substrate Filtering by the Active Site Crossover Loop in UCHL3 Revealed by Sortagging and Gain-of-function Mutations.
  J Biol Chem, 284, 3593-3602.  
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.  
18599482 B.J.Winborn, S.M.Travis, S.V.Todi, K.M.Scaglione, P.Xu, A.J.Williams, R.E.Cohen, J.Peng, and H.L.Paulson (2008).
The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains.
  J Biol Chem, 283, 26436-26443.  
18241885 D.Zhang, S.Raasi, and D.Fushman (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.
PDB codes: 2jy5 2jy6
18482987 F.E.Reyes-Turcu, J.R.Shanks, D.Komander, and K.D.Wilkinson (2008).
Recognition of polyubiquitin isoforms by the multiple ubiquitin binding modules of isopeptidase T.
  J Biol Chem, 283, 19581-19592.  
18281465 H.Tran, F.Hamada, T.Schwarz-Romond, and M.Bienz (2008).
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.
  Genes Dev, 22, 528-542.  
18799622 L.Xu, M.E.Sowa, J.Chen, X.Li, S.P.Gygi, and J.W.Harper (2008).
An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex.
  Mol Biol Cell, 19, 5059-5071.  
18438605 W.Li, and Y.Ye (2008).
Polyubiquitin chains: functions, structures, and mechanisms.
  Cell Mol Life Sci, 65, 2397-2406.  
17355622 T.Woelk, S.Sigismund, L.Penengo, and S.Polo (2007).
The ubiquitination code: a signalling problem.
  Cell Div, 2, 11.  
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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