Molecular mechanism of Mad2 conformational conversion promoted by the Mad2-interaction motif of Cdc20.

ABSTRACT: During mitosis, unattached kinetochores trigger the spindle assembly checkpoint by promoting the assembly of the mitotic checkpoint complex, a heterotetramer comprising Mad2, Cdc20, BubR1, and Bub3. Critical to this process is the kinetochore-mediated catalysis of an intrinsically slow conformational conversion of Mad2 from an open (O-Mad2) inactive state to a closed (C-Mad2) active state bound to Cdc20. These Mad2 conformational changes involve substantial remodeling of the N-terminal β1 strand and C-terminal β7/β8 hairpin. In vitro, the Mad2-interaction motif (MIM) of Cdc20 (Cdc20^MIM) triggers the rapid conversion of O-Mad2 to C-Mad2, effectively removing the kinetic barrier for MCC assembly. How Cdc20^MIM directly induces Mad2 conversion remains unclear. In this stu

SUBMITTER: Yu CWH 

PROVIDER: S-EPMC11947619 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature