Regulated protein associations govern signal transduction pathways. Distinct, small domains of much larger proteins are often responsible for the interactions. In thinking about the molecular-structural basis for specificity, it is useful to distinguish “surface–surface association” from “peptide–surface association.” The former mode is familiar from protomer contacts in oligomeric enzymes: the apposition of complementary surfaces from two folded subunits. Each surface usually contains residues from more than one segment of polypeptide chain. Small G proteins probably recognize their effectors in this manner, as suggested by the structure of Rap1 complexed with a binding domain from Raf (