Synergistic interactions of lipids and myelin basic protein
Synergistic interactions of lipids and myelin basic protein
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DOI：
10.1073/pnas.0405665101
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发表时间：
2004-09-14
影响因子：
11.1
通讯作者：
Israelachvili, J
中科院分区：
文献类型：
--
作者：
Hu, YF;Doudevski, I;Israelachvili, J
这份报告描述了力测量和原子力显微镜成像的脂质-蛋白质相互作用，确定模型膜系统的结构，密切模仿髓鞘。我们的研究结果表明，非共价，主要是静电和疏水，相互作用是负责髓鞘的多层结构和稳定性。我们发现，髓鞘碱性蛋白作为两个并列的双层之间的脂质耦合器，并作为脂质“洞填料”，有效地防止缺陷孔的发展。从我们的蛋白质介导的粘附和力距离测量，我们开发了一个简单的定量模型，给出了一个合理的准确的图片的分子机制和粘附的双层桥接蛋白通过非共价相互作用。结果和模型表明，最佳的髓鞘粘附和稳定性取决于之间的差异，而不是产品的，相反的电荷的脂质双层和髓鞘碱性蛋白，以及与膜流动性相关的排斥力，以及在这些参数的任何一个小的变化远离协同最佳值可能会导致大的变化的粘附，甚至其完全消除。我们的研究结果还表明，经常被问及的问题，膜物种，脂质或蛋白质，是“重要的”可能是错位的。两种组分协同工作以提供粘附力和整体结构。更好地理解这种协同作用的机制可以更好地理解堆叠的，特别是髓鞘膜结构，并可能导致更好地治疗脱髓鞘疾病，如多发性硬化症。
This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid "hole-filler," effectively preventing defect holes from developing. From our protein-mediated-adhesion and force-distance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the "important ones" may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.