Structural basis of human separase regulation by securin and CDK1-cyclin B1.

ABSTRACT: In early mitosis, the duplicated chromosomes are held together by the ring-shaped cohesin complex¹. Separation of chromosomes during anaphase is triggered by separase-a large cysteine endopeptidase that cleaves the cohesin subunit SCC1 (also known as RAD21^2-4). Separase is activated by degradation of its inhibitors, securin⁵ and cyclin B⁶, but the molecular mechanisms of separase regulation are not clear. Here we used cryogenic electron microscopy to determine the structures of human separase in complex with either securin or CDK1-cyclin B1-CKS1. In both complexes, separase is inhibited by pseudosubstrate motifs that block substrate binding at the catalytic site and at nearby docking sites. As in Caenorhabditis elegans⁷ and yeast⁸

SUBMITTER: Yu J 

PROVIDER: S-EPMC8482764 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature