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关于多不饱和脂肪酸在G蛋白偶联膜受体功能中作用的生物物理研究见解。

Insights from biophysical studies on the role of polyunsaturated fatty acids for function of G-protein coupled membrane receptors.

作者信息

Gawrisch Klaus, Soubias Olivier, Mihailescu Mihaela

机构信息

Section of NMR, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH, Bethesda, MD 20892, USA.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):131-4. doi: 10.1016/j.plefa.2008.09.002. Epub 2008 Nov 11.

Abstract

The composition of the lipid matrix is critical for function of membrane proteins. Perhaps one of the best studied examples is the function of the G-protein-coupled membrane receptor (GPCR) rhodopsin which is located in membranes with high content of phospholipids with polyunsaturated docosahexaenoic acid chains (DHA, 22:6n-3). Technological advances enabled a more detailed study of structure and dynamics of DHA chains and their interaction with rhodopsin. It was established that polyunsaturated DHA differs from saturated and monounsaturated hydrocarbon chains by far more rapid structural conversions. Furthermore, DHA chains tend to have higher density near the lipid/water interface while density of saturated chains is higher in the bilayer center. The interface of rhodopsin has a small number of sites for tighter interaction with DHA. Polyunsaturated phosphatidylethanolamines accumulate preferentially near the protein. Surprisingly, the high conformational freedom of most DHA chains is not measurably reduced upon interaction with rhodopsin. While some observations point at an involvement of continuum elastic properties of membranes in modulation of rhodopsin function, there is growing evidence for a role of weakly specific DHA-rhodopsin interactions.

摘要

脂质基质的组成对于膜蛋白的功能至关重要。也许研究得最透彻的例子之一是G蛋白偶联膜受体(GPCR)视紫红质的功能,它位于富含带有多不饱和二十二碳六烯酸链(DHA,22:6n - 3)的磷脂的膜中。技术进步使得对DHA链的结构和动力学及其与视紫红质的相互作用进行更详细的研究成为可能。已经确定,多不饱和DHA与饱和和单不饱和烃链的不同之处在于其结构转换要快得多。此外,DHA链在脂质/水界面附近往往具有更高的密度,而饱和链在双层中心的密度更高。视紫红质的界面有少量与DHA紧密相互作用的位点。多不饱和磷脂酰乙醇胺优先在蛋白质附近积累。令人惊讶的是,大多数DHA链的高构象自由度在与视紫红质相互作用时并没有明显降低。虽然一些观察结果表明膜的连续弹性特性参与了视紫红质功能的调节,但越来越多的证据表明弱特异性DHA - 视紫红质相互作用也发挥了作用。

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