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胆固醇含量的多不饱和脂质膜的结构和动力学研究通过中子衍射和 NMR。

Structure and dynamics of cholesterol-containing polyunsaturated lipid membranes studied by neutron diffraction and NMR.

机构信息

Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.

出版信息

J Membr Biol. 2011 Jan;239(1-2):63-71. doi: 10.1007/s00232-010-9326-6. Epub 2010 Dec 14.

DOI:10.1007/s00232-010-9326-6
PMID:21161517
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3030944/
Abstract

A direct and quantitative analysis of the internal structure and dynamics of a polyunsaturated lipid bilayer composed of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0-22:6n3-PC) containing 29 mol% cholesterol was carried out by neutron diffraction, (2)H-NMR and (13)C-MAS NMR. Scattering length distribution functions of cholesterol segments as well as of the sn-1 and sn-2 hydrocarbon chains of 18:0-22:6n3-PC were obtained by conducting experiments with specifically deuterated cholesterol and lipids. Cholesterol orients parallel to the phospholipids, with the A-ring near the lipid glycerol and the terminal methyl groups 3 Å away from the bilayer center. Previously, we reported that the density of polyunsaturated docosahexaenoic acid (DHA, 22:6n3) chains was higher near the lipid-water interface. Addition of cholesterol partially redistributes DHA density from near the lipid-water interface to the center of the hydrocarbon region. Cholesterol raises chain-order parameters of both stearic acid and DHA chains. The fractional order increase for stearic acid methylene carbons C(8)-C(18) is larger, reflecting the redistribution of DHA chain density toward the bilayer center. The correlation times of DHA chain isomerization are short and mostly unperturbed by the presence of cholesterol. The uneven distribution of saturated and polyunsaturated chain densities and the cholesterol-induced balancing of chain distributions may have important implications for the function and integrity of membrane receptors, such as rhodopsin.

摘要

通过中子衍射、(2)H-NMR 和 (13)C-MAS NMR,对由 1-硬脂酰-2-二十二碳六烯酰-sn-甘油-3-磷酸胆碱(18:0-22:6n3-PC)组成的多不饱和脂质双层的内部结构和动力学进行了直接和定量分析,该脂质双层含有 29mol%胆固醇。通过对胆固醇和脂质进行特定氘化的实验,获得了胆固醇片段以及 sn-1 和 sn-2 烃链的散射长度分布函数。胆固醇平行于磷脂取向,A 环靠近脂质甘油,末端甲基距双层中心 3Å。以前,我们报道过多不饱和二十二碳六烯酸 (DHA,22:6n3) 链的密度在靠近脂水界面处较高。胆固醇的添加部分将 DHA 密度从靠近脂水界面重新分布到烃区的中心。胆固醇提高了硬脂酸和 DHA 链的链有序参数。硬脂酸亚甲基碳原子 C(8)-C(18)的分数阶增加更大,反映了 DHA 链密度向双层中心的重新分布。DHA 链异构化的相关时间短,且大部分不受胆固醇的影响。饱和和多不饱和链密度的不均匀分布以及胆固醇诱导的链分布平衡可能对膜受体(如视紫红质)的功能和完整性具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/2b4ffc3d2d22/232_2010_9326_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/a0435cfb1f9d/232_2010_9326_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/bd02d8a0dbc3/232_2010_9326_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/043a4088f3bc/232_2010_9326_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/58a319fd551d/232_2010_9326_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/2b4ffc3d2d22/232_2010_9326_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/a0435cfb1f9d/232_2010_9326_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/bd02d8a0dbc3/232_2010_9326_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/043a4088f3bc/232_2010_9326_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/58a319fd551d/232_2010_9326_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a52/3030944/2b4ffc3d2d22/232_2010_9326_Fig5_HTML.jpg

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