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肾上腺素能受体分子内相互作用的鉴定

Identification of intramolecular interactions in adrenergic receptors.

作者信息

Suryanarayana S, von Zastrow M, Kobilka B K

机构信息

Howard Hughes Medical Institute, Stanford University Medical Center, California 94305.

出版信息

J Biol Chem. 1992 Nov 5;267(31):21991-4.

PMID:1331041
Abstract

Adrenergic receptors are representative of a large family of plasma membrane receptors that interact with G proteins during the process of transmembrane signal transduction. G protein-coupled receptors have a primary structure that is homologous to bacteriorhodopsin and are proposed to have a similar three-dimensional structure; however, it has not yet been possible to examine this hypothesis experimentally. We have used a novel mutagenesis approach to identify intramolecular interactions. Our results indicate that specific amino acids in the seventh hydrophobic segment of alpha 2 and beta 2 adrenergic receptors lie adjacent to the first hydrophobic segment. These studies provide the first experimental evidence defining spatial relationships that exist in the three-dimensional structure of adrenergic receptors.

摘要

肾上腺素能受体是一大类质膜受体的代表,它们在跨膜信号转导过程中与G蛋白相互作用。G蛋白偶联受体具有与细菌视紫红质同源的一级结构,并被认为具有相似的三维结构;然而,目前尚无法通过实验检验这一假设。我们采用了一种新的诱变方法来鉴定分子内相互作用。我们的结果表明,α2和β2肾上腺素能受体第七个疏水片段中的特定氨基酸与第一个疏水片段相邻。这些研究提供了首个实验证据,确定了肾上腺素能受体三维结构中存在的空间关系。

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1
Identification of intramolecular interactions in adrenergic receptors.肾上腺素能受体分子内相互作用的鉴定
J Biol Chem. 1992 Nov 5;267(31):21991-4.
2
Molecular biology of adrenergic receptors: model systems for the study of G-protein-mediated signal transduction.肾上腺素能受体的分子生物学:用于研究G蛋白介导的信号转导的模型系统。
Blood Vessels. 1991;28(1-3):93-103. doi: 10.1159/000158848.
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Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists.α2A - 肾上腺素能受体的定点诱变:鉴定参与配体结合及激动剂激活受体的氨基酸
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Amino acid substitutions at position 312 in the seventh hydrophobic segment of the beta 2-adrenergic receptor modify ligand-binding specificity.
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Phenylalanine in the second membrane-spanning domain of alpha 1A-adrenergic receptor determines subtype selectivity of dihydropyridine antagonists.α1A - 肾上腺素能受体第二个跨膜结构域中的苯丙氨酸决定二氢吡啶拮抗剂的亚型选择性。
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Site-directed mutagenesis of the human beta3-adrenoceptor--transmembrane residues involved in ligand binding and signal transduction.人β3-肾上腺素能受体的定点诱变——参与配体结合和信号转导的跨膜残基
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Adrenoceptors and their second messenger systems.肾上腺素能受体及其第二信使系统。
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Characterization of alpha- and beta-adrenergic receptors linked to human platelet adenylate cyclase.与人类血小板腺苷酸环化酶相关的α-和β-肾上腺素能受体的特性
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[Principle of cooperation in the receptor function of the cytoplasmic membranes].[细胞质膜受体功能中的合作原理]
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Correlated mutations and subtype specificity in the adrenergic receptor.肾上腺素能受体中的相关突变与亚型特异性
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引用本文的文献

1
Structural insights into adrenergic receptor function and pharmacology.肾上腺素能受体功能和药理学的结构见解。
Trends Pharmacol Sci. 2011 Apr;32(4):213-8. doi: 10.1016/j.tips.2011.02.005. Epub 2011 Mar 15.
2
Agonists induce conformational changes in transmembrane domains III and VI of the beta2 adrenoceptor.激动剂可诱导β2肾上腺素能受体跨膜结构域III和VI发生构象变化。
EMBO J. 1997 Nov 17;16(22):6737-47. doi: 10.1093/emboj/16.22.6737.
3
The transmembrane 7-alpha-bundle of rhodopsin: distance geometry calculations with hydrogen bonding constraints.
视紫红质的跨膜7α束:具有氢键约束的距离几何计算
Biophys J. 1997 May;72(5):1963-85. doi: 10.1016/S0006-3495(97)78842-8.
4
Activation-induced subcellular redistribution of Gs alpha.激活诱导的Gsα亚细胞重新分布。
Mol Biol Cell. 1996 Aug;7(8):1225-33. doi: 10.1091/mbc.7.8.1225.