Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20

Xuelian Lou, Guowei Fang, Melissa Coldiron, Yingxi Lin, Hongtao Yu, Marc W. Kirschner, Gerhard Wagner

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Abstract

The checkpoint protein Mad2 inhibits the activity of the anaphase promoting complex by sequestering Cdc20 until all chromosomes are aligned at the metaphase plate. We report the solution structure of human Mad2 and its interaction with Cdc20. Mad2 possesses a novel three-layered α/β fold with three α-helices packed between two β-sheets. Using deletion mutants we identified the minimal Mad2-binding region of human Cdc20 as a 40-residue segment immediately N-terminal to the WD40 repeats. Mutagenesis and NMR titration experiments show that a C-terminal flexible region of Mad2 is required for binding to Cdc20. Mad2 and Cdc20 form a tight 1:1 heterodimeric complex in which the C-terminal segment of Mad2 becomes folded. These results provide the first structural insight into mechanisms of the spindle assembly checkpoint.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalNature Structural Biology
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Lou, X., Fang, G., Coldiron, M., Lin, Y., Yu, H., Kirschner, M. W., & Wagner, G. (2000). Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20. Nature Structural Biology, 7(3), 224-229. https://doi.org/10.1038/73338