研究発表

Heterotrimeric guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein alpha subunit (Gα) that accelerate GDP dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent relaxation analyses to investigate the structural and dynamic properties of Gα. We show that Gα rapidly exchanges between a ground state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.