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PDBsum entry 2gmi
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protein Protein-protein interface(s) links
Ligase, human protein PDB id
2gmi

 

 

 

 

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Contents
Protein chains
152 a.a. *
135 a.a. *
76 a.a. *
Waters ×38
* Residue conservation analysis
PDB id:
2gmi
Name: Ligase, human protein
Title: Mms2/ubc13~ubiquitin
Structure: Ubiquitin-conjugating enzyme e2 13. Chain: a. Synonym: ubiquitin-protein ligase 13, ubiquitin carrier protein 13. Engineered: yes. Mutation: yes. Ubiquitin-conjugating enzyme variant mms2. Chain: b. Synonym: uev mms2. Engineered: yes.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: ubc13. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: mms2. Homo sapiens. Human.
Biol. unit: Trimer (from PQS)
Resolution:
2.50Å     R-factor:   0.237     R-free:   0.268
Authors: C.Wolberger,M.J.Eddins,C.M.Carlile,K.G.Gomez,C.M.Pickart
Key ref:
M.J.Eddins et al. (2006). Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nat Struct Mol Biol, 13, 915-920. PubMed id: 16980971 DOI: 10.1038/nsmb1148
Date:
06-Apr-06     Release date:   19-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P52490  (UBC13_YEAST) -  Ubiquitin-conjugating enzyme E2 13 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		153 a.a.
152 a.a.*
Protein chain
Pfam   ArchSchema ?
P53152  (MMS2_YEAST) -  Ubiquitin-conjugating enzyme variant MMS2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		137 a.a.
135 a.a.
Protein chain
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 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.3.2.23  - E2 ubiquitin-conjugating enzyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L- cysteine

 

 
DOI no: 10.1038/nsmb1148 Nat Struct Mol Biol 13:915-920 (2006)
PubMed id: 16980971  
 
 
Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation.
M.J.Eddins, C.M.Carlile, K.M.Gomez, C.M.Pickart, C.Wolberger.
 
  ABSTRACT  
 
Lys63-linked polyubiquitin chains participate in nonproteolytic signaling pathways, including regulation of DNA damage tolerance and NF-kappaB activation. E2 enzymes bound to ubiquitin E2 variants (UEV) are vital in these pathways, synthesizing Lys63-linked polyubiquitin chains, but how these complexes achieve specificity for a particular lysine linkage has been unclear. We have determined the crystal structure of an Mms2-Ubc13-ubiquitin (UEV-E2-Ub) covalent intermediate with donor ubiquitin linked to the active site residue of Ubc13. In the structure, the unexpected binding of a donor ubiquitin of one Mms2-Ubc13-Ub complex to the acceptor-binding site of Mms2-Ubc13 in an adjacent complex allows us to visualize at atomic resolution the molecular determinants of acceptor-ubiquitin binding. The structure reveals the key role of Mms2 in allowing selective insertion of Lys63 into the Ubc13 active site and suggests a molecular model for polyubiquitin chain elongation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The structure of the Mms2–Ubc13-Ub complex. (a) Blue, Mms2; magenta, Ubc13; orange, the covalently attached donor ubiquitin. TheC terminus of the donor ubiquitin, Gly76, is covalently attached to active site residue Ser87 of Ubc13(C87S). (b) Packing interactions between complexes in the crystal. One Mms2–Ubc13(C87S)-Ub complex is drawn as a surface representation (same coloring as in a) and an adjacent complex as ribbons (turquoise, Mms2; red, Ubc13; green, ubiquitin), to show packing in the crystal. The latter ubiquitin (green) binds in the acceptor site of the Mms2 from an adjacent complex (blue). Lys63 of this acceptor ubiquitin lies in the active site near the ester linkage. 		Figure 2.
Figure 2. Molecular details of linkage selectivity. (a) Active site of the E2 is shown with the covalent ester linkage between Ser87 of Ubc13(C87S) (magenta) and the C-terminal Gly76 of the donor ubiquitin (orange). Lys63 of the acceptor ubiquitin is in green. Electron density shown is from a simulated annealing omit map with F[o] - F[c] density contoured at 3 . Omitted residues included Gly74–Gly76 of ubiquitin, the side chain of Ser87 of Ubc13 and side chain atoms within 5 Šof the omitted residues. (b) Hydrogen bonds (dashed lines) help position the acceptor Lys63 in the active site of Ubc13 with the C terminus of the donor ubiquitin. (c) The interface between Mms2 (blue) and the acceptor ubiquitin is shown, with residues that affect acceptor-ubiquitin binding shown in turquoise for Mms2 (Ser27, Thr44, Ile57) and bright green for ubiquitin (Ile44).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 915-920) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
21540891 C.Behrends, and J.W.Harper (2011).
Constructing and decoding unconventional ubiquitin chains.
  Nat Struct Mol Biol, 18, 520-528.  
21532592 D.M.Wenzel, A.Lissounov, P.S.Brzovic, and R.E.Klevit (2011).
UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids.
  Nature, 474, 105-108.  
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
21376237 K.E.Wickliffe, S.Lorenz, D.E.Wemmer, J.Kuriyan, and M.Rape (2011).
The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2.
  Cell, 144, 769-781.  
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
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
20028738 A.Herrador, S.Herranz, D.Lara, and O.Vincent (2010).
Recruitment of the ESCRT machinery to a putative seven-transmembrane-domain receptor is mediated by an arrestin-related protein.
  Mol Cell Biol, 30, 897-907.  
20154706 A.R.Cole, L.P.Lewis, and H.Walden (2010).
The structure of the catalytic subunit FANCL of the Fanconi anemia core complex.
  Nat Struct Mol Biol, 17, 294-298.
PDB code: 3k1l
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
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.  
20399133 H.Fu, Y.L.Lin, and A.S.Fatimababy (2010).
Proteasomal recognition of ubiquitylated substrates.
  Trends Plant Sci, 15, 375-386.  
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.  
20797627 M.C.Rodrigo-Brenni, S.A.Foster, and D.O.Morgan (2010).
Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and ubiquitin.
  Mol Cell, 39, 548-559.  
20725033 S.Nakada, I.Tai, S.Panier, A.Al-Hakim, S.Iemura, Y.C.Juang, L.O'Donnell, A.Kumakubo, M.Munro, F.Sicheri, A.C.Gingras, T.Natsume, T.Suda, and D.Durocher (2010).
Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1.
  Nature, 466, 941-946.  
19822757 A.Williamson, K.E.Wickliffe, B.G.Mellone, L.Song, G.H.Karpen, and M.Rape (2009).
Identification of a physiological E2 module for the human anaphase-promoting complex.
  Proc Natl Acad Sci U S A, 106, 18213-18218.  
19706603 C.M.Carlile, C.M.Pickart, M.J.Matunis, and R.E.Cohen (2009).
Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5.
  J Biol Chem, 284, 29326-29334.  
20064473 H.B.Kamadurai, J.Souphron, D.C.Scott, D.M.Duda, D.J.Miller, D.Stringer, R.C.Piper, and B.A.Schulman (2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
  Mol Cell, 36, 1095-1102.
PDB codes: 3jvz 3jw0
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.  
19340006 J.A.Marteijn, L.T.van der Meer, J.J.Smit, S.M.Noordermeer, W.Wissink, P.Jansen, H.G.Swarts, R.G.Hibbert, T.de Witte, T.K.Sixma, J.H.Jansen, and B.A.van der Reijden (2009).
The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains.
  Leukemia, 23, 1480-1489.  
19851286 J.L.Parker, and H.D.Ulrich (2009).
Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5.
  EMBO J, 28, 3657-3666.  
19874575 M.E.Matyskiela, M.C.Rodrigo-Brenni, and D.O.Morgan (2009).
Mechanisms of ubiquitin transfer by the anaphase-promoting complex.
  J Biol, 8, 92.  
19345192 P.Xu, D.M.Duong, N.T.Seyfried, D.Cheng, Y.Xie, J.Robert, J.Rush, M.Hochstrasser, D.Finley, and J.Peng (2009).
Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation.
  Cell, 137, 133-145.  
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.  
19851334 Y.Ye, and M.Rape (2009).
Building ubiquitin chains: E2 enzymes at work.
  Nat Rev Mol Cell Biol, 10, 755-764.  
18276160 A.M.Burroughs, M.Jaffee, L.M.Iyer, and L.Aravind (2008).
Anatomy of the E2 ligase fold: implications for enzymology and evolution of ubiquitin/Ub-like protein conjugation.
  J Struct Biol, 162, 205-218.  
19091944 H.Wang, A.Matsuzawa, S.A.Brown, J.Zhou, C.S.Guy, P.H.Tseng, K.Forbes, T.P.Nicholson, P.W.Sheppard, H.Häcker, M.Karin, and D.A.Vignali (2008).
Analysis of nondegradative protein ubiquitylation with a monoclonal antibody specific for lysine-63-linked polyubiquitin.
  Proc Natl Acad Sci U S A, 105, 20197-20202.  
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.  
19043203 M.Minakawa, T.Sone, T.Takeuchi, and H.Yokosawa (2008).
Regulation of the nuclear factor (NF)-kappaB pathway by ISGylation.
  Biol Pharm Bull, 31, 2223-2227.  
18438605 W.Li, and Y.Ye (2008).
Polyubiquitin chains: functions, structures, and mechanisms.
  Cell Mol Life Sci, 65, 2397-2406.  
18485199 Z.Xu, E.Kohli, K.I.Devlin, M.Bold, J.C.Nix, and S.Misra (2008).
Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes.
  BMC Struct Biol, 8, 26.
PDB code: 2oxq
17496917 A.Adhikari, M.Xu, and Z.J.Chen (2007).
Ubiquitin-mediated activation of TAK1 and IKK.
  Oncogene, 26, 3214-3226.  
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
17919899 A.D.Capili, and C.D.Lima (2007).
Taking it step by step: mechanistic insights from structural studies of ubiquitin/ubiquitin-like protein modification pathways.
  Curr Opin Struct Biol, 17, 726-735.  
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.  
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
17632060 M.C.Rodrigo-Brenni, and D.O.Morgan (2007).
Sequential E2s drive polyubiquitin chain assembly on APC targets.
  Cell, 130, 127-139.  
17709375 M.D.Petroski, X.Zhou, G.Dong, S.Daniel-Issakani, D.G.Payan, and J.Huang (2007).
Substrate modification with lysine 63-linked ubiquitin chains through the UBC13-UEV1A ubiquitin-conjugating enzyme.
  J Biol Chem, 282, 29936-29945.  
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
17803232 S.Qin, and H.X.Zhou (2007).
A holistic approach to protein docking.
  Proteins, 69, 743-749.  
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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