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PDBsum entry 2fuh

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protein Protein-protein interface(s) links
Ligase PDB id
2fuh
Jmol
Contents
Protein chains
146 a.a. *
76 a.a. *
* Residue conservation analysis
PDB id:
2fuh
Name: Ligase
Title: Solution structure of the ubch5c/ub non-covalent complex
Structure: Ubiquitin-conjugating enzyme e2 d3. Chain: a. Fragment: ubch5c. Synonym: ubiquitin-protein ligase d3, ubiquitin carrier protein d3, ubiquitin-conjugating enzyme e2-17 kda 3, e217, kb 3. Engineered: yes. Ubiquitin. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ube2d3, ubch5c. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Rattus norvegicus. Norway rat. Organism_taxid: 10116.
NMR struc: 10 models
Authors: P.S.Brzovic,A.Lissounov,D.W.Hoyt,R.E.Klevit
Key ref:
P.S.Brzovic et al. (2006). A UbcH5/Ubiquitin Noncovalent Complex Is Required for Processive BRCA1-Directed Ubiquitination. Mol Cell, 21, 873-880. PubMed id: 16543155 DOI: 10.1016/j.molcel.2006.02.008
Date:
26-Jan-06     Release date:   28-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61077  (UB2D3_HUMAN) -  Ubiquitin-conjugating enzyme E2 D3
Seq:
Struc:
147 a.a.
146 a.a.
Protein chain
Pfam   ArchSchema ?
P0CG48  (UBC_HUMAN) -  Polyubiquitin-C
Seq:
Struc:
 
Seq:
Struc:
685 a.a.
76 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: E.C.6.3.2.19  - Ubiquitin--protein ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine
ATP
+ ubiquitin
+ protein lysine
= AMP
+ diphosphate
+ protein N-ubiquityllysine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   6 terms 
  Biological process     TRIF-dependent toll-like receptor signaling pathway   26 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.molcel.2006.02.008 Mol Cell 21:873-880 (2006)
PubMed id: 16543155  
 
 
A UbcH5/Ubiquitin Noncovalent Complex Is Required for Processive BRCA1-Directed Ubiquitination.
P.S.Brzovic, A.Lissounov, D.E.Christensen, D.W.Hoyt, R.E.Klevit.
 
  ABSTRACT  
 
Protein ubiquitination is a powerful regulatory modification that influences nearly every aspect of eukaryotic cell biology. The general pathway for ubiquitin (Ub) modification requires the sequential activities of a Ub-activating enzyme (E1), a Ub transfer enzyme (E2), and a Ub ligase (E3). The E2 must recognize both the E1 and a cognate E3 in addition to carrying activated Ub. These central functions are performed by a topologically conserved alpha/beta-fold core domain of approximately 150 residues shared by all E2s. However, as presented herein, the UbcH5 family of E2s can also bind Ub noncovalently on a surface well removed from the E2 active site. We present the solution structure of the UbcH5c/Ub noncovalent complex and demonstrate that this noncovalent interaction permits self-assembly of activated UbcH5c approximately Ub molecules. Self-assembly has profound consequences for the processive formation of polyubiquitin (poly-Ub) chains in ubiquitination reactions directed by the breast and ovarian cancer tumor susceptibility protein BRCA1.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of the UbcH5c/Ub Noncovalent Complex
Figure 4.
Figure 4. Self-Assembly of UbcH5c vert, similar Ub
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 21, 873-880) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22842904 A.Plechanovová, E.G.Jaffray, M.H.Tatham, J.H.Naismith, and R.T.Hay (2012).
Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis.
  Nature, 489, 115-120.
PDB code: 4ap4
22902369 H.Dou, L.Buetow, G.J.Sibbet, K.Cameron, and D.T.Huang (2012).
BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer.
  Nat Struct Mol Biol, 19, 876-883.
PDB code: 4auq
23142976 S.E.Kaiser, K.Mao, A.M.Taherbhoy, S.Yu, J.L.Olszewski, D.M.Duda, I.Kurinov, A.Deng, T.D.Fenn, D.J.Klionsky, and B.A.Schulman (2012).
Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.
  Nat Struct Mol Biol, 19, 1242-1249.
PDB codes: 4gsj 4gsk 4gsl
20967475 A.Atipairin, B.Canyuk, and A.Ratanaphan (2011).
Substitution of aspartic acid with glutamic acid at position 67 of the BRCA1 RING domain retains ubiquitin ligase activity and zinc(II) binding with a reduced transition temperature.
  J Biol Inorg Chem, 16, 217-226.  
21453497 A.Lass, R.Cocklin, K.M.Scaglione, M.Skowyra, S.Korolev, M.Goebl, and D.Skowyra (2011).
The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2.
  Cell Div, 6, 7.  
21857666 A.Plechanovová, E.G.Jaffray, S.A.McMahon, K.A.Johnson, I.Navrátilová, J.H.Naismith, and R.T.Hay (2011).
Mechanism of ubiquitylation by dimeric RING ligase RNF4.
  Nat Struct Mol Biol, 18, 1052-1059.
PDB code: 2xeu
21474069 A.Saha, S.Lewis, G.Kleiger, B.Kuhlman, and R.J.Deshaies (2011).
Essential role for ubiquitin-ubiquitin-conjugating enzyme interaction in ubiquitin discharge from Cdc34 to substrate.
  Mol Cell, 42, 75-83.  
21396940 I.Bosanac, L.Phu, B.Pan, I.Zilberleyb, B.Maurer, V.M.Dixit, S.G.Hymowitz, and D.S.Kirkpatrick (2011).
Modulation of K11-linkage formation by variable loop residues within UbcH5A.
  J Mol Biol, 408, 420-431.
PDB code: 3ptf
21422291 R.G.Hibbert, A.Huang, R.Boelens, and T.K.Sixma (2011).
E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6.
  Proc Natl Acad Sci U S A, 108, 5590-5595.
PDB codes: 2yb6 2ybf
20975996 A.Caceres, F.Shang, E.Wawrousek, Q.Liu, O.Avidan, A.Cvekl, Y.Yang, A.Haririnia, A.Storaska, D.Fushman, J.Kuszak, E.Dudek, D.Smith, and A.Taylor (2010).
Perturbing the ubiquitin pathway reveals how mitosis is hijacked to denucleate and regulate cell proliferation and differentiation in vivo.
  PLoS One, 5, e13331.  
20696387 A.Pastore (2010).
Further insights into the ubiquitin pathway: understanding the scarlet letter code.
  Structure, 18, 891-892.  
21158740 D.M.Wenzel, K.E.Stoll, and R.E.Klevit (2010).
E2s: structurally economical and functionally replete.
  Biochem J, 433, 31-42.  
20152160 E.Sakata, T.Satoh, S.Yamamoto, Y.Yamaguchi, M.Yagi-Utsumi, E.Kurimoto, K.Tanaka, S.Wakatsuki, and K.Kato (2010).
Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of the self-assembled E2~Ub conjugates.
  Structure, 18, 138-147.
PDB code: 3a33
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
20133640 I.Levin, C.Eakin, M.P.Blanc, R.E.Klevit, S.I.Miller, and P.S.Brzovic (2010).
Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub conjugate recognized by a pathogenic bacterial E3 ligase.
  Proc Natl Acad Sci U S A, 107, 2848-2853.  
  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.  
21102611 J.R.Gareau, and C.D.Lima (2010).
The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition.
  Nat Rev Mol Cell Biol, 11, 861-871.  
20017557 K.A.Nordquist, Y.N.Dimitrova, P.S.Brzovic, W.B.Ridenour, K.A.Munro, S.E.Soss, R.M.Caprioli, R.E.Klevit, and W.J.Chazin (2010).
Structural and functional characterization of the monomeric U-box domain from E4B.
  Biochemistry, 49, 347-355.
PDB code: 2kr4
19913553 L.Kundrat, and L.Regan (2010).
Identification of residues on Hsp70 and Hsp90 ubiquitinated by the cochaperone CHIP.
  J Mol Biol, 395, 587-594.  
20029420 M.S.Huen, S.M.Sy, and J.Chen (2010).
BRCA1 and its toolbox for the maintenance of genome integrity.
  Nat Rev Mol Cell Biol, 11, 138-148.  
20852628 N.Popov, C.Schülein, L.A.Jaenicke, and M.Eilers (2010).
Ubiquitylation of the amino terminus of Myc by SCF(β-TrCP) antagonizes SCF(Fbw7)-mediated turnover.
  Nat Cell Biol, 12, 973-981.  
  20081365 Q.Cheng, and J.Chen (2010).
Mechanism of p53 stabilization by ATM after DNA damage.
  Cell Cycle, 9, 472-478.  
20696396 R.C.Benirschke, J.R.Thompson, Y.Nominé, E.Wasielewski, N.Juranić, S.Macura, S.Hatakeyama, K.I.Nakayama, M.V.Botuyan, and G.Mer (2010).
Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4.
  Structure, 18, 955-965.
PDB codes: 2kre 3l1x 3l1y 3l1z
20030582 V.Nagy, and I.Dikic (2010).
Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity.
  Biol Chem, 391, 163-169.  
20495563 Y.L.Deribe, T.Pawson, and I.Dikic (2010).
Post-translational modifications in signal integration.
  Nat Struct Mol Biol, 17, 666-672.  
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.  
19604471 J.Wang, and B.A.Schulman (2009).
(G2)BRinging an E2 to E3.
  Structure, 17, 916-917.  
19887645 M.Mo, S.B.Fleming, and A.A.Mercer (2009).
Cell cycle deregulation by a poxvirus partial mimic of anaphase-promoting complex subunit 11.
  Proc Natl Acad Sci U S A, 106, 19527-19532.  
19816404 Q.Cheng, L.Chen, Z.Li, W.S.Lane, and J.Chen (2009).
ATM activates p53 by regulating MDM2 oligomerization and E3 processivity.
  EMBO J, 28, 3857-3867.  
19465916 Q.Yin, S.C.Lin, B.Lamothe, M.Lu, Y.C.Lo, G.Hura, L.Zheng, R.L.Rich, A.D.Campos, D.G.Myszka, M.J.Lenardo, B.G.Darnay, and H.Wu (2009).
E2 interaction and dimerization in the crystal structure of TRAF6.
  Nat Struct Mol Biol, 16, 658-666.
PDB codes: 3hcs 3hct 3hcu
19560420 R.Das, J.Mariano, Y.C.Tsai, R.C.Kalathur, Z.Kostova, J.Li, S.G.Tarasov, R.L.McFeeters, A.S.Altieri, X.Ji, R.A.Byrd, and A.M.Weissman (2009).
Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78.
  Mol Cell, 34, 674-685.
PDB code: 3h8k
19489725 R.J.Deshaies, and C.A.Joazeiro (2009).
RING domain E3 ubiquitin ligases.
  Annu Rev Biochem, 78, 399-434.  
19690564 S.J.van Wijk, S.J.de Vries, P.Kemmeren, A.Huang, R.Boelens, A.M.Bonvin, and H.T.Timmers (2009).
A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system.
  Mol Syst Biol, 5, 295.  
19153604 S.V.Todi, B.J.Winborn, K.M.Scaglione, J.R.Blount, S.M.Travis, and H.L.Paulson (2009).
Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3.
  EMBO J, 28, 372-382.  
19223579 W.Li, D.Tu, L.Li, T.Wollert, R.Ghirlando, A.T.Brunger, and Y.Ye (2009).
Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.
  Proc Natl Acad Sci U S A, 106, 3722-3727.
PDB code: 3fsh
19851334 Y.Ye, and M.Rape (2009).
Building ubiquitin chains: E2 enzymes at work.
  Nat Rev Mol Cell Biol, 10, 755-764.  
18851830 A.Saha, and R.J.Deshaies (2008).
Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.
  Mol Cell, 32, 21-31.  
18799573 C.R.Langelier, V.Sandrin, D.M.Eckert, D.E.Christensen, V.Chandrasekaran, S.L.Alam, C.Aiken, J.C.Olsen, A.K.Kar, J.G.Sodroski, and W.I.Sundquist (2008).
Biochemical characterization of a recombinant TRIM5alpha protein that restricts human immunodeficiency virus type 1 replication.
  J Virol, 82, 11682-11694.  
18805092 D.M.Duda, L.A.Borg, D.C.Scott, H.W.Hunt, M.Hammel, and B.A.Schulman (2008).
Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation.
  Cell, 134, 995.
PDB codes: 3dpl 3dqv
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.  
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.  
18997779 Y.Zhu, H.Li, L.Hu, J.Wang, Y.Zhou, Z.Pang, L.Liu, and F.Shao (2008).
Structure of a Shigella effector reveals a new class of ubiquitin ligases.
  Nat Struct Mol Biol, 15, 1302-1308.
PDB code: 3cvr
17956732 A.Carbia-Nagashima, J.Gerez, C.Perez-Castro, M.Paez-Pereda, S.Silberstein, G.K.Stalla, F.Holsboer, and E.Arzt (2007).
RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia.
  Cell, 131, 309-323.  
17466333 A.D.Capili, and C.D.Lima (2007).
Structure and analysis of a complex between SUMO and Ubc9 illustrates features of a conserved E2-Ubl interaction.
  J Mol Biol, 369, 608-618.
PDB code: 2pe6
17477837 B.T.Dye, and B.A.Schulman (2007).
Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.
  Annu Rev Biophys Biomol Struct, 36, 131-150.  
17392432 C.M.Eakin, M.J.Maccoss, G.L.Finney, and R.E.Klevit (2007).
Estrogen receptor alpha is a putative substrate for the BRCA1 ubiquitin ligase.
  Proc Natl Acad Sci U S A, 104, 5794-5799.  
17873885 D.E.Christensen, P.S.Brzovic, and R.E.Klevit (2007).
E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages.
  Nat Struct Mol Biol, 14, 941-948.  
17475278 D.M.Duda, R.C.van Waardenburg, L.A.Borg, S.McGarity, A.Nourse, M.B.Waddell, M.A.Bjornsti, and B.A.Schulman (2007).
Structure of a SUMO-binding-motif mimic bound to Smt3p-Ubc9p: conservation of a non-covalent ubiquitin-like protein-E2 complex as a platform for selective interactions within a SUMO pathway.
  J Mol Biol, 369, 619-630.
PDB code: 2eke
17220875 D.T.Huang, H.W.Hunt, M.Zhuang, M.D.Ohi, J.M.Holton, and B.A.Schulman (2007).
Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity.
  Nature, 445, 394-398.
PDB code: 2nvu
17426036 H.T.Kim, K.P.Kim, F.Lledias, A.F.Kisselev, K.M.Scaglione, D.Skowyra, S.P.Gygi, and A.L.Goldberg (2007).
Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages.
  J Biol Chem, 282, 17375-17386.  
17643372 J.Wang, W.Hu, S.Cai, B.Lee, J.Song, and Y.Chen (2007).
The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications.
  Mol Cell, 27, 228-237.
PDB code: 2px9
17170710 M.V.Poyurovsky, C.Priest, A.Kentsis, K.L.Borden, Z.Q.Pan, N.Pavletich, and C.Prives (2007).
The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity.
  EMBO J, 26, 90.  
17933515 P.Knipscheer, and T.K.Sixma (2007).
Protein-protein interactions regulate Ubl conjugation.
  Curr Opin Struct Biol, 17, 665-673.  
17491593 P.Knipscheer, W.J.van Dijk, J.V.Olsen, M.Mann, and T.K.Sixma (2007).
Noncovalent interaction between Ubc9 and SUMO promotes SUMO chain formation.
  EMBO J, 26, 2797-2807.
PDB code: 2uyz
17317665 S.Zhang, Y.Zhou, S.Trusa, X.Meng, E.Y.Lee, and M.Y.Lee (2007).
A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta.
  J Biol Chem, 282, 15330-15340.  
18093907 X.H.Yang, and L.Zou (2007).
Launching a ubiquitination cascade at DNA breaks.
  Proc Natl Acad Sci U S A, 104, 20645-20646.  
  20103862 Y.Chen (2007).
The enzymes in ubiquitin-like post-translational modifications.
  Biosci Trends, 1, 16-25.  
17114057 M.D.Petroski, G.Kleiger, and R.J.Deshaies (2006).
Evaluation of a diffusion-driven mechanism for substrate ubiquitination by the SCF-Cdc34 ubiquitin ligase complex.
  Mol Cell, 24, 523-534.  
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.