Switches, latches, and amplifiers: common themes of G proteins and molecular motors.

N a universe where entropy is increasing, living organisms are a curious anomaly. The organization that distinguishes living organisms from their inanimate surroundings relies upon their ability to execute vectoral processes such as directed movements, ion pumping across membranes, and the assembly of macromolecules and organelle systems. Such phenomena are executed by protein machines that harness chemical energy to drive processes that would be otherwise energetically unfavorable. Two of the best studied protein machines are the ATPhydrolyzing motor proteins and the GTP-hydrolyzing G proteins. Motor proteins (kinesins, myosins, and dyneins) move along cytoskeletal filaments and are involved in generating most of the cellular and intracellular motions that are associated with living organisms. G proteins are a diverse group of molecular switches that regulate information flow in signal transduction pathways and orchestrate an orderly sequence of interactions in protein synthesis, protein translocation across membranes, and trafficking of vesicles in the endocytotic and secretory pathways. Essential to the mechanism of both classes of proteins, the NTP and NDP bound forms of the enzymes exhibit distinct conformations, which enables them to change affinity for target proteins (cytoskeletal polymers for motors and various target proteins for G proteins). Historically, the scientific investigations of motor proteins and G proteins have proceeded along separate paths. However, many of the key questions regarding the role of nucleotide hydrolysis are the same: What is the nature of the conformational switch between NTP and NDP states? How do changes in the nucleotide-binding site affect the binding interaction with target proteins? How are the rate constants governing transitions in the nucleotidase cycle set and controlled? Recent structural and kinetic studies have uncovered intriguing parallels between molecular motors (kinesin and myosin) and G proteins which may be important for understanding these questions. The premise