The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching

Abstract

The metamorphic Mad2 protein acts as a molecular switch in the checkpoint mechanism that monitors proper chromosome attachment to spindle microtubules during cell division. The remarkably slow spontaneous rate of Mad2 switching between its checkpoint inactive and active forms is catalyzed onto a physiologically relevant time scale by a self–self interaction between its two forms, culminating in a large pool of active Mad2. Recent structural, biochemical, and cell biological advances suggest that the catalyzed conversion of Mad2 requires a major structural rearrangement that transits through a partially unfolded intermediate.