Protein chemistry at membrane interfaces: Non-additivity of electrostatic and hydrophobic interactions
Protein chemistry at membrane interfaces: Non-additivity of electrostatic and hydrophobic interactions
复制标题
DOI：
10.1006/jmbi.2001.4684
复制
发表时间：
2001-06-08
影响因子：
5.6
通讯作者：
White, SH
中科院分区：
文献类型：
--
作者：
Ladokhin, AS;White, SH
蛋白质和多肽与带电的膜界面的非特异性结合依赖于疏水(DeltaG(H Phi))和静电(DeltaG(ES))自由能的共同贡献。如果这些是简单的相加，则观察到的结合自由能(DeltaG(Obs))将由DeltaG(Obs)=DeltaG(H Phi)+DeltaG(Es)给出，其中DeltaG(H Phi)=-sigma(Np)A(Np)和DeltaG(Es)=ZF Phi。在这些表达式中，A(NP)是非极性可及区，Sigma(NP)是非极性溶剂化参数，z是形式肽价，F是法拉第常数，Phi是膜表面电势。但一些证据表明，蛋白质在膜界面的疏水和静电结合自由能，如那些与细胞信号有关的自由能，并不是简单的相加。为了系统地探讨这个问题，我们测定了吲哚青素变体的界面分配自由能，吲哚青素是一种富含脯氨酸的阳离子抗菌肽。合成的13个残基的变异体覆盖了广泛的疏水自由能，这使得我们能够研究疏水性对中性和阴离子脂类混合物形成的膜静电结合的影响。虽然DeltaG(Obs)始终是DeltaG(H Phi)的线性函数，但斜率依赖于阴离子脂类的含量：对于纯的两性离子磷胆碱双层膜，斜率为1.0，对于纯磷酸甘油膜，斜率为0.3，DeltaG(Obs)也与表面电位线性变化，但斜率小于预期值ZF。由于我们的系统方法，我们能够建立一个有用的经验法则：每增加3千卡摩尔(-1)(1千卡=4.184千焦耳)，增量G(H·Phi)的有利增加，相对于z减少约20%。对于中性磷胆碱界面，我们发现使用基于Wimley-White实验的界面疏水性标度可以非常准确地预测DeltaG(OBS)。(C)2001年学术出版社。
Non-specific binding of proteins and peptides to charged membrane interfaces depends upon the combined contributions of hydrophobic (DeltaG(H phi)) and electrostatic (DeltaG(ES)) free energies. If these are simply additive, then the observed free energy of binding (DeltaG(obs)) will be given by DeltaG(obs) = DeltaG(H Phi) + DeltaG(ES), where DeltaG(H Phi) = -sigma (NP)A(NP) and DeltaG(ES) = zF phi. Ln these expressions, A(NP) is the non-polar accessible area, sigma (NP) the non-polar solvation parameter, z the formal peptide valence, F the Faraday constant, and phi the membrane surface potential. But several Lines of evidence suggest that hydrophobic and electrostatic binding free energies of proteins at membrane interfaces, such as those associated with cell signaling, are not simply additive. In order to explore this issue systematically, we have determined the interfacial partitioning free energies of variants of indolicidin, a cationic proline-rich antimicrobial peptide. The synthesized variants of the 13 residue peptide covered a wide range of hydrophobic free energies, which allowed us to examine the effect of hydrophobicity on electrostatic binding to membranes formed from mixtures of neutral and anionic Lipids. Although DeltaG(obs) was always a linear function of DeltaG(H Phi) the slope depended upon anionic Lipid content: the slope was 1.0 for pure, zwitterionic phosphocholine bilayers and 0.3 for pure phosphoglycerol membranes, DeltaG(obs) also varied linearly with surface potential, but the slope was smaller than the expected value, zF. As observed by others, this suggests an effective peptide valence z,, that is smaller than the formal valence z. Because of our systematic approach, we were able to establish a useful rule-of-thumb: z,, is reduced relative to z by about 20 % for each 3 kcal mol(-1) (1 kcal = 4.184 kJ) favorable increase in DeltaG(H Phi). For neutral phosphocholine interfaces, we found that DeltaG(obs) could be predicted with remarkable accuracy using the Wimley-White experiment-based interfacial hydrophobicity scale. (C) 2001 Academic Press.