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PDBsum entry 1j7d

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protein Protein-protein interface(s) links
Unknown function PDB id
1j7d
Jmol
Contents
Protein chains
140 a.a. *
149 a.a. *
Waters ×190
* Residue conservation analysis
PDB id:
1j7d
Name: Unknown function
Title: Crystal structure of hmms2-hubc13
Structure: Mms2. Chain: a. Engineered: yes. Ubiquitin-conjugating enzyme e2-17 kda. Chain: b. Synonym: ubc13. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.85Å     R-factor:   0.215     R-free:   0.244
Authors: T.F.Moraes,R.A.Edwards,S.Mckenna,L.Pashushok,W.Xiao, J.N.M.Glover,M.J.Ellison
Key ref:
T.F.Moraes et al. (2001). Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13. Nat Struct Biol, 8, 669-673. PubMed id: 11473255 DOI: 10.1038/90373
Date:
16-May-01     Release date:   08-Aug-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q15819  (UB2V2_HUMAN) -  Ubiquitin-conjugating enzyme E2 variant 2
Seq:
Struc:
145 a.a.
140 a.a.
Protein chain
Pfam   ArchSchema ?
P61088  (UBE2N_HUMAN) -  Ubiquitin-conjugating enzyme E2 N
Seq:
Struc:
152 a.a.
149 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: 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     UBC13-UEV1A complex   8 terms 
  Biological process     nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway   39 terms 
  Biochemical function     protein binding     8 terms  

 

 
    reference    
 
 
DOI no: 10.1038/90373 Nat Struct Biol 8:669-673 (2001)
PubMed id: 11473255  
 
 
Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13.
T.F.Moraes, R.A.Edwards, S.McKenna, L.Pastushok, W.Xiao, J.N.Glover, M.J.Ellison.
 
  ABSTRACT  
 
The ubiquitin conjugating enzyme complex Mms2-Ubc13 plays a key role in post-replicative DNA repair in yeast and the NF-kappaB signal transduction pathway in humans. This complex assembles novel polyubiquitin chains onto yet uncharacterized protein targets. Here we report the crystal structure of a complex between hMms2 (Uev1) and hUbc13 at 1.85 A resolution and a structure of free hMms2 at 1.9 A resolution. These structures reveal that the hMms2 monomer undergoes a localized conformational change upon interaction with hUbc13. The nature of the interface provides a physical basis for the preference of Mms2 for Ubc13 as a partner over a variety of other structurally similar ubiquitin-conjugating enzymes. The structure of the hMms2-hUbc13 complex provides the conceptual foundation for understanding the mechanism of Lys 63 multiubiquitin chain assembly and for its interactions with the RING finger proteins Rad5 and Traf6.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The interface created by the hMms2 -hUbc13 complex. a, The interface of hMms2 and hUbc13 (hMms2 in yellow and hUbc13 in blue) with an 90 clockwise rotation with respect to Fig. 1. Residues in the interface are labeled (hMms2 in yellow and hUbc13 in blue). The active site Cys in hUbc13 is labeled in black. b, Sequence alignments of the interface residues in hUbc13 and hMms2 with homologs/orthologs in humans and yeast. Residues in the hMms2 -hUbc13 interface are colored in yellow and blue, respectively, and residues in the proposed hUbc13 -E3(RING) interface are colored in green. Residues in the E2 that interact with ubiquitin are colored in red. Absolutely and partially conserved residues between the E2 homologs are shaded in black and gray, respectively. Secondary structural elements are shown above (for the E2s) and below (for Uev) the sequence alignment. c, Stereo view of the experimental, MAD-phased complex to 2.0 resolution with the electron density map contoured at 1.2 . The electron density is superimposed on the refined model.
Figure 4.
Figure 4. Molecular surface of hMms2 -hUbc13 heterodimer. The molecular surface of the hMms2 and hUbc13 is shaded yellow and blue, respectively, in approximately the same orientation as Fig. 1a. The potential ubiquitin binding site and E3 RING finger-binding residues are colored in red and green, respectively, as in Fig. 2b. The hUbc13 active site Cys residue is colored yellow. Arrows indicate the clefts on either side of the heterodimer interface where the noncovalent ubiquitin may be positioned. The figure was drawn using the programs Molscript27 and GRASP28.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 669-673) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20613989 J.Scheper, M.Guerra-Rebollo, G.Sanclimens, A.Moure, I.Masip, D.González-Ruiz, N.Rubio, B.Crosas, O.Meca-Cortés, N.Loukili, V.Plans, A.Morreale, J.Blanco, A.R.Ortiz, A.Messeguer, and T.M.Thomson (2010).
Protein-protein interaction antagonists as novel inhibitors of non-canonical polyubiquitylation.
  PLoS One, 5, e11403.  
21179194 L.B.Kramer, J.Shim, M.L.Previtera, N.R.Isack, M.C.Lee, B.L.Firestein, and C.Rongo (2010).
UEV-1 is an ubiquitin-conjugating enzyme variant that regulates glutamate receptor trafficking in C. elegans neurons.
  PLoS One, 5, e14291.  
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.  
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
19028681 Y.Park, S.K.Yoon, and J.B.Yoon (2009).
The HECT Domain of TRIP12 Ubiquitinates Substrates of the Ubiquitin Fusion Degradation Pathway.
  J Biol Chem, 284, 1540-1549.  
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.  
18679808 M.G.Lerner, K.L.Meagher, and H.A.Carlson (2008).
Automated clustering of probe molecules from solvent mapping of protein surfaces: new algorithms applied to hot-spot mapping and structure-based drug design.
  J Comput Aided Mol Des, 22, 727-736.  
18321851 O.A.Bazirgan, and R.Y.Hampton (2008).
Cue1p is an activator of Ubc7p E2 activity in vitro and in vivo.
  J Biol Chem, 283, 12797-12810.  
18353733 T.Göhler, I.M.Munoz, J.Rouse, and J.J.Blow (2008).
PTIP/Swift is required for efficient PCNA ubiquitination in response to DNA damage.
  DNA Repair (Amst), 7, 775-787.  
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.  
17452636 N.Philip, and T.A.Haystead (2007).
Characterization of a UBC13 kinase in Plasmodium falciparum.
  Proc Natl Acad Sci U S A, 104, 7845-7850.  
17933515 P.Knipscheer, and T.K.Sixma (2007).
Protein-protein interactions regulate Ubl conjugation.
  Curr Opin Struct Biol, 17, 665-673.  
17108083 I.Unk, I.Hajdú, K.Fátyol, B.Szakál, A.Blastyák, V.Bermudez, J.Hurwitz, L.Prakash, S.Prakash, and L.Haracska (2006).
Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen.
  Proc Natl Acad Sci U S A, 103, 18107-18112.  
16428438 J.E.Mullally, T.Chernova, and K.D.Wilkinson (2006).
Doa1 is a Cdc48 adapter that possesses a novel ubiquitin binding domain.
  Mol Cell Biol, 26, 822-830.  
16980971 M.J.Eddins, C.M.Carlile, K.M.Gomez, C.M.Pickart, and C.Wolberger (2006).
Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation.
  Nat Struct Mol Biol, 13, 915-920.
PDB code: 2gmi
16518696 M.J.Lewis, L.F.Saltibus, D.D.Hau, W.Xiao, and L.Spyracopoulos (2006).
Structural basis for non-covalent interaction between ubiquitin and the ubiquitin conjugating enzyme variant human MMS2.
  J Biomol NMR, 34, 89.
PDB code: 1zgu
17041755 N.A.Syed, P.L.Andersen, R.C.Warrington, and W.Xiao (2006).
Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-kappaB activation.
  Apoptosis, 11, 2147-2157.  
16215985 V.Plans, J.Scheper, M.Soler, N.Loukili, Y.Okano, and T.M.Thomson (2006).
The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation.
  J Cell Biochem, 97, 572-582.  
15772086 C.Tsui, A.Raguraj, and C.M.Pickart (2005).
Ubiquitin binding site of the ubiquitin E2 variant (UEV) protein Mms2 is required for DNA damage tolerance in the yeast RAD6 pathway.
  J Biol Chem, 280, 19829-19835.  
15749714 L.Pastushok, T.F.Moraes, M.J.Ellison, and W.Xiao (2005).
A single Mms2 "key" residue insertion into a Ubc13 pocket determines the interface specificity of a human Lys63 ubiquitin conjugation complex.
  J Biol Chem, 280, 17891-17900.  
16307917 M.Zhang, M.Windheim, S.M.Roe, M.Peggie, P.Cohen, C.Prodromou, and L.H.Pearl (2005).
Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.
  Mol Cell, 20, 525-538.
PDB codes: 2c2l 2c2v
16129784 P.L.Andersen, H.Zhou, L.Pastushok, T.Moraes, S.McKenna, B.Ziola, M.J.Ellison, V.M.Dixit, and W.Xiao (2005).
Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A.
  J Cell Biol, 170, 745-755.  
14747994 B.M.Kus, C.E.Caldon, R.Andorn-Broza, and A.M.Edwards (2004).
Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro.
  Proteins, 54, 455-467.  
15062086 C.Dominguez, A.M.Bonvin, G.S.Winkler, F.M.van Schaik, H.T.Timmers, and R.Boelens (2004).
Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches.
  Structure, 12, 633-644.
PDB code: 1ur6
15044434 H.Teo, D.B.Veprintsev, and R.L.Williams (2004).
Structural insights into endosomal sorting complex required for transport (ESCRT-I) recognition of ubiquitinated proteins.
  J Biol Chem, 279, 28689-28696.
PDB code: 1uzx
15328341 N.Merkley, and G.S.Shaw (2004).
Solution structure of the flexible class II ubiquitin-conjugating enzyme Ubc1 provides insights for polyubiquitin chain assembly.
  J Biol Chem, 279, 47139-47147.
PDB code: 1tte
15465811 R.B.Dodd, M.D.Allen, S.E.Brown, C.M.Sanderson, L.M.Duncan, P.J.Lehner, M.Bycroft, and R.J.Read (2004).
Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal domain reveals a Novel E2-binding C4HC3-type RING domain.
  J Biol Chem, 279, 53840-53847.
PDB code: 1vyx
15461659 T.Tenno, K.Fujiwara, H.Tochio, K.Iwai, E.H.Morita, H.Hayashi, S.Murata, H.Hiroaki, M.Sato, K.Tanaka, and M.Shirakawa (2004).
Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains.
  Genes Cells, 9, 865-875.  
15053872 W.I.Sundquist, H.L.Schubert, B.N.Kelly, G.C.Hill, J.M.Holton, and C.P.Hill (2004).
Ubiquitin recognition by the human TSG101 protein.
  Mol Cell, 13, 783-789.
PDB code: 1s1q
12944097 B.R.Wong, F.Parlati, K.Qu, S.Demo, T.Pray, J.Huang, D.G.Payan, and M.K.Bennett (2003).
Drug discovery in the ubiquitin regulatory pathway.
  Drug Discov Today, 8, 746-754.  
12644454 B.Wang, S.L.Alam, H.H.Meyer, M.Payne, T.L.Stemmler, D.R.Davis, and W.I.Sundquist (2003).
Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4.
  J Biol Chem, 278, 20225-20234.
PDB code: 1nj3
12496280 H.D.Ulrich (2003).
Protein-protein interactions within an E2-RING finger complex. Implications for ubiquitin-dependent DNA damage repair.
  J Biol Chem, 278, 7051-7058.  
12535537 M.A.Verdecia, C.A.Joazeiro, N.J.Wells, J.L.Ferrer, M.E.Bowman, T.Hunter, and J.P.Noel (2003).
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.
  Mol Cell, 11, 249-259.
PDB code: 1nd7
12900394 O.Pornillos, D.S.Higginson, K.M.Stray, R.D.Fisher, J.E.Garrus, M.Payne, G.P.He, H.E.Wang, S.G.Morham, and W.I.Sundquist (2003).
HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein.
  J Cell Biol, 162, 425-434.  
14517261 P.Y.Wu, M.Hanlon, M.Eddins, C.Tsui, R.S.Rogers, J.P.Jensen, M.J.Matunis, A.M.Weissman, A.M.Weisman, A.M.Weissman, C.Wolberger, C.P.Wolberger, and C.M.Pickart (2003).
A conserved catalytic residue in the ubiquitin-conjugating enzyme family.
  EMBO J, 22, 5241-5250.  
12569095 S.McKenna, T.Moraes, L.Pastushok, C.Ptak, W.Xiao, L.Spyracopoulos, and M.J.Ellison (2003).
An NMR-based model of the ubiquitin-bound human ubiquitin conjugation complex Mms2.Ubc13. The structural basis for lysine 63 chain catalysis.
  J Biol Chem, 278, 13151-13158.  
12431996 Y.Xia, G.M.Pao, H.W.Chen, I.M.Verma, and T.Hunter (2003).
Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein.
  J Biol Chem, 278, 5255-5263.  
12226657 C.Hoege, B.Pfander, G.L.Moldovan, G.Pyrowolakis, and S.Jentsch (2002).
RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO.
  Nature, 419, 135-141.  
12354763 K.P.Bencsath, M.S.Podgorski, V.R.Pagala, C.A.Slaughter, and B.A.Schulman (2002).
Identification of a multifunctional binding site on Ubc9p required for Smt3p conjugation.
  J Biol Chem, 277, 47938-47945.  
12379843 O.Pornillos, S.L.Alam, D.R.Davis, and W.I.Sundquist (2002).
Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein.
  Nat Struct Biol, 9, 812-817.
PDB codes: 1m4p 1m4q
12006492 O.Pornillos, S.L.Alam, R.L.Rich, D.G.Myszka, D.R.Davis, and W.I.Sundquist (2002).
Structure and functional interactions of the Tsg101 UEV domain.
  EMBO J, 21, 2397-2406.
PDB codes: 1kpp 1kpq
12531181 T.R.Pray, F.Parlati, J.Huang, B.R.Wong, D.G.Payan, M.K.Bennett, S.D.Issakani, S.Molineaux, and S.D.Demo (2002).
Cell cycle regulatory E3 ubiquitin ligases as anticancer targets.
  Drug Resist Updat, 5, 249-258.  
11927573 Y.Lin, W.C.Hwang, and R.Basavappa (2002).
Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.
  J Biol Chem, 277, 21913-21921.
PDB code: 1i7k
12408865 Y.Liu, L.Fallon, H.A.Lashuel, Z.Liu, and P.T.Lansbury (2002).
The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility.
  Cell, 111, 209-218.  
11917106 Z.Li, W.Xiao, J.J.McCormick, and V.M.Maher (2002).
Identification of a protein essential for a major pathway used by human cells to avoid UV- induced DNA damage.
  Proc Natl Acad Sci U S A, 99, 4459-4464.  
11583613 C.M.Pickart (2001).
Ubiquitin enters the new millennium.
  Mol Cell, 8, 499-504.  
11504715 S.McKenna, L.Spyracopoulos, T.Moraes, L.Pastushok, C.Ptak, W.Xiao, and M.J.Ellison (2001).
Noncovalent interaction between ubiquitin and the human DNA repair protein Mms2 is required for Ubc13-mediated polyubiquitination.
  J Biol Chem, 276, 40120-40126.  
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.