IDENTIFICATION OF A RECEPTOR G-PROTEIN CONTACT SITE CRITICAL FOR SIGNALING SPECIFICITY AND G-PROTEIN ACTIVATION
IDENTIFICATION OF A RECEPTOR G-PROTEIN CONTACT SITE CRITICAL FOR SIGNALING SPECIFICITY AND G-PROTEIN ACTIVATION
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DOI：
10.1073/pnas.92.25.11642
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发表时间：
1995-12-05
影响因子：
11.1
通讯作者：
WESS, J
中科院分区：
文献类型：
--
作者：
LIU, J;CONKLIN, BR;WESS, J
每个G蛋白偶联受体只能识别细胞内表达的许多结构密切相关的G蛋白的一个独特子集。这种选择性是如何在分子水平上实现的还不是很清楚，特别是因为没有确定受体与其同源G蛋白之间特定的点对点接触位点。在这项研究中，我们证明了m2毒菌碱乙酰胆碱受体（一种典型的G（i/o）偶联受体）上的一个4-aa表位可以特异性识别G（i/o）蛋白家族α亚基的c -末端5aa。据预测，参与这种相互作用的m2受体残基位于第三胞内环和第六跨膜结构域交界处的α -螺旋受体区域的一侧。杂交m2/m3毒蕈碱受体和突变g蛋白α (q)亚基的共表达研究表明，本研究确定的受体/ g蛋白接触位点对于偶联特异性和g蛋白激活至关重要。
Each G protein-coupled receptor recognizes only a distinct subset of the many structurally closely related G proteins expressed within a cell. How this selectivity is achieved at a molecular level is not well understood, particularly since no specific point-to point contact sites between a receptor and its cognate G protein(s) have been identified. In this study, we demonstrate that a 4-aa epitope on the m2 muscarinic acetylcholine receptor, a prototypical G(i/o)-coupled receptor, can specifically recognize the C-terminal 5 aa of alpha subunits of the G(i/o) protein family. The m2 receptor residues involved in this interaction are predicted to be located on one side of an alpha-helical receptor region present at the junction between the third intracellular loop and the sixth transmembrane domain. Coexpression studies with hybrid m2/m3 muscarinic receptors and mutant G-protein alpha(q), subunits showed that the receptor/G-protein contact site identified in this study is essential for coupling specificity and G-protein activation.