Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers.
Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers.
复制标题
DOI：
10.1085/jgp.104.4.645
复制
发表时间：
1994-10
期刊：
影响因子：
--
通讯作者：
Andersen OS
中科院分区：
文献类型：
--
作者：
Lundbaek JA;Andersen OS
脂质代谢产物，游离脂肪酸和溶血磷脂，改变膜蛋白，包括离子通道的功能。这种改变可以通过信号转导途径发生，但也可能是由于代谢物对蛋白质的“直接”作用。为了研究这种直接作用的可能机制，我们研究了溶血磷脂（LPL）：溶血磷脂酰胆碱（LPC），溶血磷脂酰乙醇胺（LPE），溶血磷脂酰丝氨酸（LPS）和溶血磷脂酰肌醇（LPI）短杆菌肽通道功能的改变。实验是在由二植烷酰磷脂酰胆碱在正癸烷中形成的平面双分子膜上进行的，该系统可以排除受体介导的效应。在低于临界胶束浓度（CMC）的水溶液浓度下，LPL可以使膜结合短杆菌肽的二聚常数增加高达500倍（在2 μ M下）。相对效力作为极性头基的大小的函数而增加，但似乎不作为头基电荷的函数而变化。增加的二聚化常数主要来自通道形成的速率常数的增加，其可以增加超过100倍（在LPC和LPI的存在下），而通道解离速率常数仅降低约5倍。LPL效应不能归因于增加的膜流动性，这将引起增加的通道解离速率常数。LPC降低通道解离速率常数的能力随通道长度（其总是小于膜的平衡厚度）而变化：随着通道长度的减小，LPC的效力增加。LPC对空气/电解质界面处的膜厚度或单分子膜的表面张力没有影响。形成双层的甘油单油酸酯不降低通道解离速率常数。这些结果表明，LPL通过改变膜变形能来改变短杆菌肽通道功能，并且变形能的变化可以与膜修饰化合物的分子“形状”相关。生物膜的机械性质的类似改变可以形成一种可以改变膜蛋白功能的一般机制。
Lipid metabolites, free fatty acids and lysophospholipids, modify the function of membrane proteins including ion channels. Such alterations can occur through signal transduction pathways, but may also result from "direct" effects of the metabolite on the protein. To investigate possible mechanisms for such direct effects, we examined the alterations of gramicidin channel function by lysophospholipids (LPLs): lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). The experiments were done on planar bilayers formed by diphytanoylphosphatidylcholine in n-decane a system where receptor- mediated effects can be excluded. At aqueous concentrations below the critical micelle concentration (CMC), LPLs can increase the dimerization constant for membrane-bound gramicidin up to 500-fold (at 2 microM). The relative potency increases as a function of the size of the polar head group, but does not seem to vary as a function of head group charge. The increased dimerization constant results primarily from an increase in the rate constant for channel formation, which can increase more than 100-fold (in the presence of LPC and LPI), whereas the channel dissociation rate constant decreases only about fivefold. The LPL effect cannot be ascribed to an increased membrane fluidity, which would give rise to an increased channel dissociation rate constant. The ability of LPC to decrease the channel dissociation rate constant varies as a function of channel length (which is always less than the membrane's equilibrium thickness): as the channel length is decreased, the potency of LPC is increased. LPC has no effect on membrane thickness or the surface tension of monolayers at the air/electrolyte interface. The bilayer-forming glycerolmonooleate does not decrease the channel dissociation rate constant. These results show that LPLs alter gramicidin channel function by altering the membrane deformation energy, and that the changes in deformation energy can be related to the molecular "shape" of the membrane-modifying compounds. Similar alterations in the mechanical properties of biological membranes may form a general mechanism by which one can alter membrane protein function.