Determinants of conformational dimerization of Mad2 and its inhibition by p31comet

摘要: The spindle assembly checkpoint (SAC) monitors chromosome attachment to microtubules. SAC proteins operate at kinetochores, scaffolds mediating chromosome-microtubule attachment. ubiquitous constituents Mad1 and Mad2 are recruited kinetochores in prometaphase. sequesters Cdc20 prevent its ability mediate anaphase onset. Its function is counteracted by p31comet (formerly CMT2). Upon binding Cdc20, changes conformation from O-Mad2 (Open) C-Mad2 (Closed). A Mad1-bound template, which binds prior being converted into Cdc20-bound C-Mad2, assists this process. molecular understanding of prion-like property missing. We characterized the determinants O-Mad2:C-Mad2 conformational dimer derived a rationalization interface terms symmetric asymmetric components. Mutation individual residues abrogates Saccharomyces cerevisiae. NMR chemical shift perturbations indicate that undergoes major rearrangement upon suggesting dimerization facilitates structural conversion required bind Cdc20. also show negative effects on based competition with for binding.