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Schlagwörter:
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Zusammenfassung:
Mad2 is an essential component of the spindle assembly checkpoint (SAC),
a molecular device designed to coordinate anaphase onset with the
completion of chromosome attachment to the spindle. Capture of
chromosome by microtubules occur on protein scaffolds known as
kinetochores. The SAC proteins are recruited to kinetochores in
prometaphase where they generate a signal that halts anaphase until all
sister chromatid pairs are bipolarly oriented. Mad2 is a subunit of the
mitotic checkpoint complex, which is regarded as the effector of the
spindle checkpoint. Its function is the sequestration of Cdc20, a
protein required for progression into anaphase. The function of Mad2 in
the checkpoint correlates with a dramatic conformational rearrangement
of the Mad2 protein. Mad2 adopts a closed conformation (C-Mad2) when
bound to Cdc20, and an open conformation (O-Mad2) when unbound to this
ligand. Checkpoint activation promotes the conversion of O-Mad2 to
Cdc20-bound C-Mad2. We show that this conversion requires a C-Mad2
template and we identify this in Mad l-bound Mad2. In our proposition,
Mad1-bound C-Mad2 recruits O-Mad2 to kinetochores, stimulating Cdc20
capture, implying that O-Mad2 and C-Mad2 form dimers. We discuss Mad2
oligomerization and link our discoveries to previous observations
related to Mad2 oligomerization.
