Abstract
Membrane-bound G proteins carry information from receptors on the outside of cells to effector proteins inside cells. The α subunits of these heterotrimeric proteins bind and hydrolyse GTP and control the specificity of interactions with receptor and effector elements1,2. Signalling by G proteins involves a cycle in which the inactive αβγ-GDP complex dissociates to produce α*-GTP, which is capable of activating the effector enzyme or ion channel; the α*-GTP complex hydrolyses bound GTP and reassociates with βγ to form the inactive complex. We have characterized a mutation that interrupts this GTP-driven cycle in αs, the α-chain of Gs, the G protein that stimulates adenylyl cyclase. The mutation converts a glycine to an alanine residue in the presumed GDP-binding domain of αs. The location and biochemical consequences of this mutation suggest a common mechanism by which binding of GTP or ATP may induce changes in the conformation of a number of nucleoside triphosphate binding proteins.
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Miller, R., Masters, S., Sullivan, K. et al. A mutation that prevents GTP-dependent activation of the α chain of Gs. Nature 334, 712–715 (1988). https://doi.org/10.1038/334712a0
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DOI: https://doi.org/10.1038/334712a0
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