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Curr Opin Struct Biol. 2018 Apr;49:114-122. doi: 10.1016/j.sbi.2018.01.012. Epub 2018 Feb 14.

Structural biology of the separase-securin complex with crucial roles in chromosome segregation.

Author information

1
Department of Biological Sciences Columbia University New York, NY 10027, USA.
2
Department of Biological Sciences Columbia University New York, NY 10027, USA. Electronic address: ltong@columbia.edu.

Abstract

The cysteine protease separase opens the cohesin ring by cleaving its kleisin subunit and is a pivotal cell cycle factor for the transition from metaphase to anaphase. It is inhibited by forming a complex with the chaperone securin, and in vertebrates, also by the Cdk1-cyclin B1 complex. Separase is activated upon the destruction of securin or cyclin B1 by the proteasome, after ubiquitination by the anaphase-promoting complex/cyclosome (APC/C). Here we review recent structures of the active protease segment of Chaetomium thermophilum separase in complex with a substrate-mimic inhibitor and full-length Saccharomyces cerevisiae and Caenorhabditis elegans separase in complex with securin. These structures define the mechanism for substrate recognition and catalysis by separase, and show that securin has extensive contacts with separase, consistent with its chaperone function. They confirm that securin inhibits separase by binding as a pseudo substrate.

PMID:
29452922
PMCID:
PMC5915870
DOI:
10.1016/j.sbi.2018.01.012
[Indexed for MEDLINE]
Free PMC Article

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