NMR STRUCTURE OF A RECEPTOR-BOUND G-PROTEIN PEPTIDE
NMR STRUCTURE OF A RECEPTOR-BOUND G-PROTEIN PEPTIDE
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DOI：
10.1038/363276a0
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发表时间：
1993-05-20
期刊：
影响因子：
64.8
通讯作者：
HAMM, HE
中科院分区：
文献类型：
--
作者：
DRATZ, EA;FURSTENAU, JE;HAMM, HE
异源三聚体GTP结合蛋白（G蛋白）通过与激素或感觉受体偶联来调节细胞活性。受刺激的受体催化GDP从G蛋白α-亚基1 -4释放，与空α-亚基结合的GTP提供控制效应物如腺苷酸环化酶、磷酸二酯酶、磷脂酶和离子通道4的信号。活化受体的三个胞质环被认为与异源三聚体G蛋白上的三个位点相互作用，以提供高亲和力相互作用并催化G蛋白活化5 -8。α-亚基的羧基末端对于与受体的相互作用特别重要9 -14。在这里，我们研究的结构之间的光子受体视紫红质和G蛋白转导，或G（t），使用核磁共振活性界面的一部分。来自G（t）α-亚基C末端的11个氨基酸肽（α（t）（340-350））结合视紫红质并模拟G蛋白以稳定其活性形式，即后视紫红质II。肽α（t）（340-350）与兴奋和未兴奋的视紫红质结合，两种结合形式之间的构象差异表明激动剂刺激的受体激活G蛋白的机制。深入了解受体催化的GDP释放将具有广泛的应用，因为GTP/GDP交换和GTP结合蛋白的内在GTP酶活性构成了广泛的调节机制15。
HETEROTRIMERIC GTP-binding proteins (G proteins) regulate cellular activity by coupling to hormone or sensory receptors. Stimulated receptors catalyse the release of GDP from G protein alpha-subunits1-4 and GTP bound to the empty alpha-subunits provides signals that control effectors such as adenylyl cyclases, phosphodiesterases, phospholipases and ion channels4. Three cytoplasmic loops of the activated receptor are thought to interact with three sites on the heterotrimeric G protein to provide high-affinity interaction and catalyse G-protein activation5-8. The carboxyl terminus of the alpha-subunit is particularly important for interaction with the receptor9-14. Here we study the structure of part of the active interface between the photon receptor rhodopsin and the G protein transducin, or G(t), using nuclear magnetic resonance. An 11-amino-acid peptide from the C terminus of the alpha-subunit of G(t) (alpha(t) (340-350)) binds to rhodopsin and mimics the G protein in stabilizing its active form, metarhodopsin II. The peptide alpha(t) (340-350) binds to both excited and unexcited rhodopsin and conformational differences between the two bound forms suggest a mechanism for activation of G proteins by agonist-stimulated receptors. Insight into receptor-catalysed GDP release will have broad application because the GTP/GDP exchange and the intrinsic GTPase activity of GTP-binding proteins constitute a widespread regulatory mechanism15.