Unifying Family A GPCR Theories of Activation

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• 作者：Benjamin G. Tehan ; ^{ben.tehan@heptares.com" class="auth_mail} ; Andrea Bortolato ; Frank E. Blaney ; Malcolm P. Weir ; Jonathan S. Mason
• 关键词：GPCR ; Activation ; Constitutive activity ; Conservational analysis
• 刊名：Pharmacology and Therapeutics
• 出版年：July, 2014
• 年：2014
• 卷：143
• 期：1
• 页码：51-60
• 全文大小：1559 K

文摘

Several new pairs of active and inactive GPCR structures have recently been solved enabling detailed structural insight into the activation process, not only of rhodopsin but now also of the 尾₂ adrenergic, M₂ muscarinic and adenosine A_2A receptors. Combined with structural analyses they have enabled us to examine the different recent theories proposed for GPCR activation and show that they are all indeed parts of the same process, and are intrinsically related through their effect on the central hydrophobic core of GPCRs. This new unifying general process of activation is consistent with the identification of known constitutively active mutants and an in-depth conservational analysis of significant residues implicated in the process.