IDENTIFICATION OF RECEPTOR CONTACT SITE INVOLVED IN RECEPTOR-G PROTEIN COUPLING
IDENTIFICATION OF RECEPTOR CONTACT SITE INVOLVED IN RECEPTOR-G PROTEIN COUPLING
复制标题
DOI：
10.1038/330758a0
复制
发表时间：
1987-12-24
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：
SULLIVAN, KA;MILLER, RT;BOURNE, HR
哺乳动物G蛋白将来自细胞外信号（包括神经递质、激素和感觉刺激）的信息传递到细胞内效应酶或离子通道的调节中。由适当的细胞外信号触发，受体蛋白通过在鸟嘌呤核苷酸结合位点催化GTP取代GDP来特异性激活G蛋白家族的成员。像受体蛋白1，异源三聚体G蛋白表现出令人印象深刻的结构相似性2，3，这表明所有的受体-G蛋白相互作用使用同源的结构元件和一个单一的分子机制。因此，每个G蛋白的拓扑等价部分可以与适当的受体相互作用。我们最近预测了复合G蛋白α链的二级结构，并提出在多肽的羧基末端预测的两亲性α螺旋直接接触受体4。这一建议现在已经通过对野生型细胞和突变小鼠S49淋巴瘤细胞系unc中编码腺苷酸环化酶刺激调节因子（Gs）α链（αs）的基因的互补DNA进行测序得到证实，其中Gs不能被激素受体激活5。这些序列揭示了unc基因中的一个点突变，该点突变将α s多肽羧基末端附近的一个精氨酸取代为一个脯氨酸残基。α s基因缺陷型S49细胞表达重组αs-uncin可复制uncin表型。
The mammalian G proteins transduce information from extracellular signals, including neurotransmitters, hormones and sensory stimuli, into regulation of effector enzymes or ion channels within cells. Triggered by appropriate extracellular signals, receptor proteins specifically activate members of the G protein family by catalysing replacement of GDP by GTP at the guanine nucleotide binding site. Like the receptor proteins1, the heterotrimeric G proteins exhibit impressive structural similarities2,3, suggesting that all receptor–G protein interactions use homologous structural elements and a single molecular mechanism. Topologically equivalent portions of each G protein may therefore interact with the appropriate receptor. We recently predicted the secondary structure of a composite G protein α-chain and proposed that a predicted amphipathic α-helix at the extreme carboxy-terminus of the polypeptide directly contacts receptors4. This proposal has now been confirmed by sequencing complementary DNAs of the gene that encodes the α-chain (αs) of the stimulatory regulator (Gs) of adenylyl cyclase in wild-type cells and in a mutant mouse S49 lymphoma cell line,unc, in which Gscannot be activated by hormone receptors5. The sequences reveal a point mutation in theuncgene that substitutes a proline residue for an arginine near the carboxy-terminus of the αs-polypeptide. Expression of recombinant αs-uncin genetically αs-deficient S49 cells reproduces theuncphenotype.