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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases*
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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DNA Helicases
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Fungal Proteins / chemistry
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Fungal Proteins / metabolism
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Humans
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Ligases / chemistry*
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Ligases / metabolism*
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Structure, Secondary
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Proteins / chemistry
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Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Structure-Activity Relationship
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Substrate Specificity
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TNF Receptor-Associated Factor 6
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Trans-Activators / chemistry*
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Trans-Activators / metabolism*
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Ubiquitin-Conjugating Enzymes
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Ubiquitins / metabolism
Substances
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Fungal Proteins
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Macromolecular Substances
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Proteins
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Saccharomyces cerevisiae Proteins
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TNF Receptor-Associated Factor 6
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Trans-Activators
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Ubiquitins
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UBE2V2 protein, human
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Ubiquitin-Conjugating Enzymes
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Adenosine Triphosphatases
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RAD5 protein, S cerevisiae
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DNA Helicases
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Ligases