Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13.
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.
Moraes
T F
TF
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G-2H7, Canada.
Edwards
R A
RA
McKenna
S
S
Pastushok
L
L
Xiao
W
W
Glover
J N
JN
Ellison
M J
MJ
D000251:Adenosine Triphosphatases; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004265:DNA Helicases; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D048029:TNF Receptor-Associated Factor 6; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism
D005656:Fungal Proteins; D046911:Macromolecular Substances; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D048029:TNF Receptor-Associated Factor 6; D015534:Trans-Activators; D014452:Ubiquitins; C114715:UBE2V2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases; D008025:Ligases