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Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2–hUbc13

Nature Structural Biology volume 8, pages 669–673 (2001)Cite this article

Abstract

The ubiquitin conjugating enzyme complex Mms2–Ubc13 plays a key role in post-replicative DNA repair in yeast and the NF-κB 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 Å resolution and a structure of free hMms2 at 1.9 Å 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.

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Figure 1: The overall structure of the hMms2–hUbc13 complex.
Figure 2: The interface created by the hMms2–hUbc13 complex.
Figure 3: Comparison of free and bound forms of hMms2.
Figure 4: Molecular surface of hMms2–hUbc13 heterodimer.

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Acknowledgements

We wish to thank R. Sweet and the staff of the beamline X12C (NSLS) for technical support during crystallographic data collection. We also thank members of the Ellison and Glover labs for valuable discussions and S. Smith for secretarial services. This work was supported by a research grant from the National Cancer Institute of Canada (M.J.E) and Canadian Institutes of Health Research (J.N.M.G and W.X.). W.X. is a research scientist of the National Cancer Institute of Canada.

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Authors and Affiliations

  1. Department of Biochemistry, University of Alberta, Edmonton, T6G-2H7, Alberta, Canada

    Trevor F. Moraes, Ross A. Edwards, Sean McKenna, J.N. Mark Glover & Michael J. Ellison

  2. Department of Microbiology, University of Saskatchewan, Saskatoon, S7N-5E5, Canada

    Landon Pastushok & Wei Xiao

  3. Institute for Biomolecular Design, University of Alberta, Edmonton, T6G-2H7, Alberta, Canada

    J.N. Mark Glover & Michael J. Ellison

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  1. Trevor F. Moraes
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Correspondence to J.N. Mark Glover or Michael J. Ellison.

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Moraes, T., Edwards, R., McKenna, S. et al. Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2–hUbc13. Nat Struct Mol Biol 8, 669–673 (2001). https://doi.org/10.1038/90373

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