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Insights into anaphase promoting complex TPR subdomain assembly from a CDC26–APC6 structure

Nature Structural & Molecular Biology volume 16, pages 987–989 (2009)Cite this article

Abstract

The multisubunit anaphase promoting complex (APC) is an essential cell-cycle regulator. Although CDC26 is known to have a role in APC assembly, its molecular function has remained unclear. Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity. Notably, CDC26–APC6 association involves an intermolecular TPR mimic composed of one helix from each protein.

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Figure 1: CDC26 stabilizes APC6 structure.
Figure 2: CDC26N–APC6TPR interactions and yeast complementation.

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Acknowledgements

We are indebted to D. King (Howard Hughes Medical Institute Mass Spectrometry Laboratory), S. Otieno and R. Kriwacki for assistance with CD, C. Ross and D. Miller for computational support and D.W. Miller and S. Bozeman for administration. This work was funded by the American Lebanese Syrian Associated Charities (ALSAC), the US National Institutes of Health (NIH) (P30CA021765 to St. Jude Cancer Center), a Beckman Young Investigator Award to B.A.S. and the Howard Hughes Medical Institute. NECAT beamlines (Advanced Photon Source (APS)) are supported by RR-15301 from the National Center for Research Resources at NIH. APS is supported by the US Department of Energy, Office of Basic Energy Sciences, contract W-31-109-ENG-38. B.A.S. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Departments of Structural Biology and Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Jing Wang, Billy T Dye & Brenda A Schulman

  2. Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Billy T Dye & Brenda A Schulman

  3. Department of Chemistry and Chemical Biology, Cornell University, NE-CAT, Advanced Photon Source, Argonne, Illinois, USA

    Kanagalaghatta R Rajashankar & Igor Kurinov

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  1. Jing Wang
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  2. Billy T Dye
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  3. Kanagalaghatta R Rajashankar
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Contributions

J.W. designed, performed and analyzed biochemical, biophysical and crystallography experiments and wrote the manuscript; B.T.D. designed, performed and analyzed biochemical and yeast genetic experiments and wrote the manuscript; K.R.R. and I.K. performed and analyzed crystallography experiments; B.A.S. advised on all aspects of the project and wrote the manuscript.

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Correspondence to Brenda A Schulman.

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Supplementary Figures 1–6, Supplementary Table 1 and Supplementary Methods (PDF 4843 kb)

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Wang, J., Dye, B., Rajashankar, K. et al. Insights into anaphase promoting complex TPR subdomain assembly from a CDC26–APC6 structure. Nat Struct Mol Biol 16, 987–989 (2009). https://doi.org/10.1038/nsmb.1645

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