Binding takes cooperation

The CDK inhibitor Sic1 gets proteolyzed in late G1, but the regulation of its binding to the Cdc4 ubiquitin ligase subunit has been a conundrum. The proteins do not bind unless Sic1 is phosphorylated on at least six of its nine sites, yet Cdc4 can harbor only one phosphorylated epitope. Traditional thermodynamic arguments cannot explain this puzzle, but a new mathematical model from Peter Klein (Fox Run Management, Greenwich, CT), Tony Pawson, and Mike Tyers (University of Toronto, Toronto, Canada) offers an explanation.

The group imagined that additional binding sites might make Sic1 more likely to rebind at another site than to diffuse away from Cdc4. “It's like seaweed floating in the waves,” says Klein. “Pieces get stuck on a rock. A wave might knock it off, but before it floats away, another arm...