Crystal structure of the adenylyl cyclase activator G(S alpha)
Crystal structure of the adenylyl cyclase activator G(S alpha)
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DOI：
10.1126/science.278.5345.1943
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发表时间：
1997-12-12
期刊：
影响因子：
56.9
通讯作者：
Sprang, SR
中科院分区：
文献类型：
--
作者：
Sunahara, RK;Tesmer, JJG;Sprang, SR
G（S α）（刺激腺苷酸环化酶的异源三聚体G蛋白α亚基）的晶体结构在2.5埃与鸟苷5 '-O-（3-硫代三磷酸）（GTP γ S）的复合物中测定。G（S α）是GTP结合蛋白家族的原型成员，其以酶依赖性方式调节效应物的活性。G（S α）.GTP γ S与G（i α）.GTP γ S的结构的比较表明，它们的效应子特异性主要由开关II螺旋和α 3-β 5环形成的结合表面的形状决定，尽管这些元件具有高度的序列同源性。相比之下，序列差异解释了G蛋白信号调节剂不能刺激G（S α）的GT3活性。G（S α）的β-γ结合表面在序列和结构上与G（i α）的β-γ结合表面很大程度上是保守的，而羧基末端螺旋和α 4-β 6环形成的表面差异可能介导受体特异性。
The crystal structure of G(S alpha), the heterotrimeric G protein alpha subunit that stimulates adenylyl cyclase, was determined at 2.5 Angstrom in a complex with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). G(S alpha) is the prototypic member of a family of GTP-binding proteins that regulate the activities of effectors in a hormone-dependent manner. Comparison of the structure of G(S alpha).GTP gamma S with that of G(i alpha).GTP gamma S suggests that their effector specificity is primarily dictated by the shape of the binding surface formed by the switch II helix and the alpha 3-beta 5 loop, despite the high sequence homology of these elements. In contrast, sequence divergence explains the inability of regulators of G protein signaling to stimulate the GTPase activity of G(S alpha). The beta gamma binding surface of G(S alpha) is largely conserved in sequence ana structure to that of G(i alpha), whereas differences in the surface formed by the carboxyl-terminal helix and the alpha 4-beta 6 loop may mediate receptor specificity.