Docosahexaenoic acid alters bilayer elastic properties
Docosahexaenoic acid alters bilayer elastic properties
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DOI：
10.1073/pnas.0701015104
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发表时间：
2007-06-05
影响因子：
11.1
通讯作者：
Andersen, Olaf S.
中科院分区：
文献类型：
--
作者：
Bruno, Michael J.;Koeppe, Roger E., II;Andersen, Olaf S.
在低微摩尔浓度下，多不饱和脂肪酸（PUFAs）会改变许多膜蛋白的功能。PUFAs在相似浓度下对不相关的蛋白质发挥作用，表明它们具有共同的作用模式。由于脂质双分子层是膜蛋白的共同“溶剂”，其共同机制可能是PUFAs吸附在双分子层/溶液界面上，促进脂质固有曲率的负变化，并像其他可逆吸附的两亲分子一样，增加双分子层的弹性。因此，PUFA吸附会改变与蛋白质/双层边界构象变化相关的双层变形能，这将改变蛋白质的功能。为了探索这一机制的可行性，我们使用了不同长度的gramicidin （gA）类似物和不同厚度的双层来评估二十二碳六烯酸（DHA）是否可以通过双层介导的机制发挥作用。事实上，DHA增加了gA通道的出现率和寿命，并降低了通道形成的自由能。出现率和寿命变化随通道-双层疏水失配的增加而增加，与不同的DHA双层吸收系数无关。因此，DHA改变了双层的弹性特性，而不仅仅是脂质固有的曲率；弹性变化对DHA的双分子层修饰作用很重要。对膜蛋白功能影响不大的油酸（OA）的吸附系数比DHA大一个数量级，但对膜蛋白的功能没有影响。这些结果表明，DHA（和其他PUFAs）可能通过双分子层介导的机制调节膜蛋白功能，这种机制不涉及特定的蛋白质结合，而是涉及双分子层材料特性的改变。
At low micromolar concentrations, polyunsaturated fatty acids (PUFAs) alter the function of many membrane proteins. PUFAs exert their effects on unrelated proteins at similar concentrations, suggesting a common mode of action. Because lipid bilayers serve as the common "solvent" for membrane proteins, the common mechanism could be that PUFAs adsorb to the bilayer/solution interface to promote a negative-going change in lipid intrinsic curvature and, like other reversibly adsorbing amphiphiles, increase bilayer elasticity. PUFA adsorption thus would alter the bilayer deformation energy associated with protein conformational changes involving the protein/bilayer boundary, which would alter protein function. To explore the feasibility of such a mechanism, we used gramicidin (gA) analogues of different lengths together with bilayers of different thicknesses to assess whether docosahexaenoic acid (DHA) could exert its effects through a bilayer-mediated mechanism. Indeed, DHA increases gA channel appearance rates and lifetimes and decreases the free energy of channel formation. The appearance rate and lifetime changes increase with increasing channel-bilayer hydrophobic mismatch and are not related to differing DHA bilayer absorption coefficients. DHA thus alters bilayer elastic properties, not just lipid intrinsic curvature; the elasticity changes are important for DHA's bilayer-modifying actions. Oleic acid (OA), which has little effect on membrane protein function, exerts no such effects despite OA's adsorption coefficient being an order of magnitude greater than DHA's. These results suggest that DHA (and other PUFAs) may modulate membrane protein function by bilayer-mediated mechanisms that do not involve specific protein binding but rather changes in bilayer material properties.