Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles
Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles
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DOI：
10.1016/s0006-3495(97)78203-1
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发表时间：
1997-10-01
影响因子：
3.4
通讯作者：
McLaughlin, S
中科院分区：
文献类型：
--
作者：
BenTal, N;Honig, B;McLaughlin, S
我们先前将泊松-玻尔兹曼方程应用于磷脂双层和基本肽的原子模型，以根据第一原理计算它们的静电相互作用（Ben-Tal，N.，B。霍尼希河M.佩奇湾Denisov和S.麦克拉夫兰1996.小的碱性肽与含有酸性脂质的膜的结合。理论模型和实验结果。Biophys. J. 71：561-575）。具体地，我们计算了简单碱性肽（例如，五赖氨酸）与磷脂囊泡。理论预测与结合的实验测量吻合得很好，但这种一致可能是偶然的，因为这些柔性肽的结构尚不清楚。在这里，我们使用相同的理论方法来计算膜结合的两个小的蛋白质的已知结构：charybdotoxin（CTx）和iberiotoxin（IbTx），我们还测量这些蛋白质的结合磷脂囊泡。理论模型准确地描述了K对CTx（净电荷+4）和IbTx（净电荷+2）的离子强度和膜中酸性脂质摩尔%的依赖性。例如，该理论正确地预测，K值的CTx的结合膜含有33%的酸性脂质应减少10（5）的因素时，盐浓度从10增加到200 mM。我们讨论的理论方法的局限性，也考虑了一个简单的扩展，将非极性相互作用的理论。
We previously applied the Poisson-Boltzmann equation to atomic models of phospholipid bilayers and basic peptides to calculate their electrostatic interactions from first principles (Ben-Tal, N., B. Honig, R. M. Peitzsch, G. Denisov, and S. McLaughlan. 1996. Binding of small basic peptides to membranes containing acidic lipids. Theoretical models and experimental results. Biophys. J. 71:561-575). Specifically, we calculated the molar partition coefficient, K (the reciprocal of the lipid concentration at which 1/2 the peptide is bound), of simple basic peptides (e.g., pentalysine) with phospholipid vesicles. The theoretical predictions agreed well with experimental measurements of the binding, but the agreement could have been fortuitous because the structure(s) of these flexible peptides is not known. Here we use the same theoretical approach to calculate the membrane binding of two small proteins of known structure: charybdotoxin (CTx) and iberiotoxin (IbTx); we also measure the binding of these proteins to phospholipid vesicles. The theoretical model describes accurately the dependence of K on the ionic strength and mol % acidic lipid in the membrane for both CTx (net charge +4) and IbTx (net charge +2). For example, the theory correctly predicts that the value of K for the binding of CTx to a membrane containing 33% acidic lipid should decrease by a factor of 10(5) when the salt concentration increases from 10 to 200 mM. We discuss the limitations of the theoretical approach and also consider a simple extension of the theory that incorporates nonpolar interactions.