A MUTATION THAT PREVENTS GTP-DEPENDENT ACTIVATION OF THE ALPHA-CHAIN OF GS
A MUTATION THAT PREVENTS GTP-DEPENDENT ACTIVATION OF THE ALPHA-CHAIN OF GS
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DOI：
10.1038/334712a0
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发表时间：
1988-08-25
期刊：
影响因子：
64.8
通讯作者：
BOURNE, HR
中科院分区：
文献类型：
--
作者：
MILLER, RT;MASTERS, SB;BOURNE, HR
膜结合 G 蛋白将信息从细胞外部的受体传递到细胞内的效应蛋白。这些异源三聚体蛋白的 α 亚基结合并水解 GTP，并控制与受体和效应元件相互作用的特异性1,2。 G 蛋白的信号传导涉及一个循环，其中无活性的 αβγ-GDP 复合物解离产生 α*-GTP，能够激活效应酶或离子通道； α*-GTP 复合物水解结合的 GTP 并与 βγ 重新结合形成无活性的复合物。我们已经鉴定出一种突变，它会中断 αs 中这种 GTP 驱动的循环，即 Gs 的 α 链，即刺激腺苷酸环化酶的 G 蛋白。该突变将假定的 αs GDP 结合域中的甘氨酸残基转化为丙氨酸残基。这种突变的位置和生化后果表明了一种常见机制，GTP 或 ATP 的结合可能通过这种机制诱导许多核苷三磷酸结合蛋白的构象发生变化。
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.