Role of cholesterol in ligand binding and G-protein coupling of serotonin1A receptors solubilized from bovine hippocampus
Role of cholesterol in ligand binding and G-protein coupling of serotonin1A receptors solubilized from bovine hippocampus
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DOI：
10.1016/j.bbrc.2004.12.102
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发表时间：
2005-02-25
影响因子：
3.1
通讯作者：
Harikumar, KG
中科院分区：
文献类型：
--
作者：
Chattopadhyay, A;Jafurulla, M;Harikumar, KG
5-羟色胺（serotonin，IA）（5-HTIA）受体是七跨膜结构域G蛋白偶联受体超家族的重要成员。我们在这里报告，溶解的海马5-HTIA受体的两性离子洗涤剂CHAPS是伴随着膜胆固醇的损失，这导致在特定的激动剂结合活性和G-蛋白偶联的程度降低。重要的是，使用MbetaCD-胆固醇复合物将胆固醇补充到溶解的膜，恢复了膜的胆固醇含量，并显著增强了特异性激动剂结合活性和G蛋白偶联。这些新的结果提供了有用的信息，胆固醇在溶解G-蛋白偶联受体，这些受体的分子表征的重要步骤的作用。(C)2004年爱思唯尔公司All rights reserved.
The serotonin(IA) (5-HTIA) receptor is an important member of the superfamily of seven transmembrane domain G-protein-coupled receptors. We report here that solubilization of the hippocampal 5-HTIA receptor by the zwitterionic detergent CHAPS is accompanied by loss of membrane cholesterol which results in a reduction in specific agonist binding activity and extent of G-protein coupling. Importantly, replenishment of cholesterol to solubilized membranes using MbetaCD-cholesterol complex restores the cholesterol content of the membrane and significantly enhances the specific agonist binding activity and G-protein coupling. These novel results provide useful information on the role of cholesterol in solubilization of G-protein-coupled receptors, an important step for molecular characterization of these receptors. (C) 2004 Elsevier Inc. All rights reserved.