The two faces of Mad2

Sequence dictates structure, but for Mad2, one structure is not enough. New results from groups led by Hongtao Yu and Josep Rizo (University of Texas Southwestern, Dallas, TX) show that Mad2 adopts two distinct conformations and that checkpoint activation may consist of switching Mad2 to the right form.Mad2 holds up anaphase until every chromosome is properly attached to the spindle. Past structural studies of Mad2 showed that Mad1 (its activator), and Cdc20 (its anaphase-halting target) share the same binding site. “It would seem,” says Rizo, “that [Mad1] would be a competitor rather than an activator because they bind in the same place.” But the newly identified second conformation suggests an answer to this puzzle–Mad1 may put Mad2 in an active conformation that is maintained even when the Mads separate.

The two forms can be distinguished...