Organization and functions of interacting domains for signaling by protein-protein interactions

Information transfer from activated heterotrimeric guanine nucleotide-binding proteins (G proteins) to downstream effectors occurs through noncovalent protein-protein interactions. Such interactions involve multiple regions of contact between the G protein and the effector. Some of these regions mediate information transfer, as defined by their ability to change the activity of their downstream binding partners, whereas other interactions appear to contribute solely to binding affinity. Such modular configurations occur in functionally diverse proteins such as myosin and a regulator of the double-stranded DNA stimulated protein kinase (PKR) called PACT. In most cases, it appears that both charge complementarity and the architecture of the interacting surfaces provide the appropriate balance between specificity of interactions and their reversibility. Information transfer regions appear to display conformational flexibility in interactions. Such flexible interactions may be essential for the local conformational changes necessary to induce change in activity by an induced fit-type mechanism. Thus, a general mechanism for information transfer by protein-protein interactions could use specific regions that induce conformation changes in the downstream partner. Other binding regions may be arranged within the protein to impart specificity of recognition and thereby maintain overall contact between the partners during the conformational dynamics that occur in the signal-transfer process.