Binding of basic peptides to acidic lipids in membranes: effects of inserting alanine(s) between the basic residues.
Binding of basic peptides to acidic lipids in membranes: effects of inserting alanine(s) between the basic residues.
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DOI：
10.1021/bi00121a026
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发表时间：
1992-02
期刊：
影响因子：
2.9
通讯作者：
Marian Mosior;Stuart McLaughlin
中科院分区：
文献类型：
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作者：
Marian Mosior;Stuart McLaughlin
我们研究了含有五个基本残基的肽与含有酸性脂质的膜的结合。多肽具有5个精氨酸或赖氨酸残基和0、1或2个碱性基团之间的丙氨酸。这些囊泡由两性离子脂质、磷脂酰胆碱和酸性脂质（磷脂酰丝氨酸或磷脂酰甘油）的混合物形成。使用平衡透析、超滤和电泳迁移技术测量结合，我们发现所有肽与膜的结合与酸性脂质的摩尔分数呈s型依赖关系。s型依赖性（希尔系数大于1或表观协同性）是由于静电和维数的降低，可以用一个简单的模型来描述，该模型结合了Gouy-Chapman-Stern理论和质量作用形式主义。该模型中可调参数为碱性残基与酸性脂质的微观关联常数k（1小于k小于10 M-1）。丙氨酸残基的加入降低了多肽对膜的亲和力；在碱基残基之间插入两个丙氨酸可使k降低2倍。同样，肽对膜的亲和力降低了10倍，这可能是由于局部静电效应和更大质量的含丙氨酸肽与膜结合时可能发生的熵损失增加的共同作用。精氨酸肽比赖氨酸肽结合更强：精氨酸残基的k比赖氨酸残基高2倍。我们的研究结果表明，如果一簇精氨酸和赖氨酸残基与散布的电中性氨基酸结合在一起，如果该簇含有5个以上的基本残基，则可以将细胞质蛋白的很大一部分结合到质膜上。
We studied the binding of peptides containing five basic residues to membranes containing acidic lipids. The peptides have five arginine or lysine residues and zero, one, or two alanines between the basic groups. The vesicles were formed from mixtures of a zwitterionic lipid, phosphatidylcholine, and an acidic lipid, either phosphatidylserine or phosphatidylglycerol. Measuring the binding using equilibrium dialysis, ultrafiltration, and electrophoretic mobility techniques, we found that all peptides bind to the membranes with a sigmoidal dependence on the mole fraction of acidic lipid. The sigmoidal dependence (Hill coefficient greater than 1 or apparent cooperativity) is due to both electrostatics and reduction of dimensionality and can be described by a simple model that combines Gouy-Chapman-Stern theory with mass action formalism. The adjustable parameter in this model is the microscopic association constant k between a basic residue and an acidic lipid (1 less than k less than 10 M-1). The addition of alanine residues decreases the affinity of the peptides for the membranes; two alanines inserted between the basic residues reduces k 2-fold. Equivalently, the affinity of the peptide for the membrane decreases 10-fold, probably due to a combination of local electrostatic effects and the increased loss of entropy that may occur when the more massive alanine-containing peptides bind to the membrane. The arginine peptides bind more strongly than the lysine peptides: k for an arginine residue is 2-fold higher than for a lysine residue. Our results imply that a cluster of arginine and lysine residues with interspersed electrically neutral amino acids can bind a significant fraction of a cytoplasmic protein to the plasma membrane if the cluster contains more than five basic residues.