How the dynamic properties and functional mechanisms of GPCRs are modulated by their coupling to the membrane environment.
How the dynamic properties and functional mechanisms of GPCRs are modulated by their coupling to the membrane environment.
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GPCR 的动态特性和功能机制如何通过与膜环境的耦合来调节。
DOI：
10.1007/978-94-007-7423-0_4
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发表时间：
2014
影响因子：
--
通讯作者：
Weinstein,Harel
中科院分区：
文献类型：
--
作者：
Mondal,Sayan;Khelashvili,George;Johner,Niklaus;Weinstein,Harel
Experimental observations of the dependence of function and organization of G protein-coupled receptors (GPCRs) on their lipid environment have stimulated new quantitative studies of the coupling between the proteins and the membrane. It is important to develop such a quantitative understanding at the molecular level because the effects of the coupling are seen to be physiologically and clinically significant. Here we review findings that offer insight into how membrane-GPCR coupling is connected to the structural characteristics of the GPCR, from sequence to 3D structural detail, and how this coupling is involved in the actions of ligands on the receptor. The application of a recently developed computational approach designed for quantitative evaluation of membrane remodeling and the energetics of membrane-protein interactions brings to light the importance of the radial asymmetry of the membrane-facing surface of GPCRs in their interaction with the surrounding membrane. As the radial asymmetry creates adjacencies of hydrophobic and polar residues at specific sites of the GPCR, the ability of membrane remodeling to achieve complete hydrophobic matching is limited, and the residual mismatch carries a significant energy cost. The adjacencies are shown to be affected by ligand-induced conformational changes. Thus, functionally important organization of GPCRs in the cell membrane can depend both on ligand-determined properties and on the lipid composition of various membrane regions with different remodeling capacities. That this functionally important reorganization can be driven by oligomerization patterns that reduce the energy cost of the residual mismatch, suggests a new perspective on GPCR dimerization and ligand-GPCR interactions. The relation between the modulatory effects on GPCRs from the binding of specific cell-membrane components, e.g., cholesterol, and those produced by the non-local energetics of hydrophobic mismatch are discussed in this context.
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视觉中的 G 蛋白偶联受体视紫红质。
DOI：
--
发表时间：
2007
期刊：
Farumashia (in press)
影响因子：
--
作者：
Takahashi;R.;et al.;H.Tsukamoto
通讯作者：
H.Tsukamoto
影响因子：
64.8
作者：
Choe, Hui-Woog;Kim, Yong Ju;Ernst, Oliver P.
通讯作者：
Ernst, Oliver P.
影响因子：
56.9
作者：
Luttrell, LM;Ferguson, SSG;Lefkowitz, RJ
通讯作者：
Lefkowitz, RJ
影响因子：
4.8
作者：
Lei, S;Liapakis, G;Javitch, JA
通讯作者：
Javitch, JA
影响因子：
11.4
作者：
Ruprecht, JJ;Mielke, T;Schertler, GFX
通讯作者：
Schertler, GFX