Membrane defects as a generalized driving force for membrane protein interactions.
Membrane defects as a generalized driving force for membrane protein interactions.
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膜缺陷作为膜蛋白相互作用的普遍驱动力。
DOI：
10.1073/pnas.2315655120
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发表时间：
2023
影响因子：
11.1
通讯作者：
Fleming,KarenG
中科院分区：
文献类型：
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作者：
Fleming,KarenG
疏水效应如何驱动埋藏在膜的非极性区域内的非极性蛋白质相互作用表面之间的结合？与本体相比，水浓度在中心双层区域（1）中低至少一百万倍，这意味着基本上没有水被释放。有趣的是，发表在PNAS（2）中的CLC-ec 1二聚化反应的热力学分析揭示了二聚体形成时的高负热容变化，这是水释放的标志性特征。疏水效应是膜蛋白双层相互作用的驱动力吗？在膜蛋白折叠中，我们预期疏水效应在多肽插入双层时表现出其力量，并且该反应是使用疏水性尺度从一级序列预测跨膜片段的基础（3）。但是，一旦插入，长期以来一直认为膜蛋白中的相互作用将主要由蛋白质界面内和蛋白质界面之间的其他力介导，如货车范德华堆积，氢键和静电相互作用（4）。当膜蛋白结合时，由于远离脂质的表面积减少，也会发生脂质链熵的增加。但这些都没有被期望涉及水的释放。尽管如此，由于与实验测量膜蛋白缔合反应相关的技术挑战，很少有数据可用于检查这些租户。
How can the hydrophobic effect drive binding between nonpolar protein interaction surfaces buried within the nonpolar regions of the membrane? Compared to bulk, the water concentration is at least a million-fold lower in the central bilayer region (1), which means that there is essentially no water to be released. Paradoxically, a thermodynamic analysis of the CLC-ec1dimerization reaction published in PNAS (2) reveals a high negative heat capacity change upon dimer formation, a hallmark signature of water release. Is the hydrophobic effect a generalized force driving bilayer interactions of membrane proteins?In membrane protein folding, we expect the hydrophobic effect to manifest its power upon insertion of polypeptides into the bilayer, and this reaction is the basis for the prediction of transmembrane segments from primary sequence using hydrophobicity scales (3). But once inserted, it has long been posited that interactions in membrane proteins would be primarily mediated by other forces within and between protein interfaces such as van der Waals packing, hydrogen bonding, and electrostatic interactions (4). Increases in lipid chain entropy will also occur as the surface area buried away from lipids decreases when membrane proteins associate. But none of these have ever been expected to involve the release of water. Still, due to the technical challenges associated with experimentally measuring membrane protein association reactions, very little data have been available to examine these tenants.