Goñi F M, Ostolaza H
Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.
Braz J Med Biol Res. 1998 Aug;31(8):1019-34. doi: 10.1590/s0100-879x1998000800002.
alpha-Hemolysin is synthesized as a 1024-amino acid polypeptide, then intracellularly activated by specific fatty acylation. A second activation step takes place in the extracellular medium through binding of Ca2+ ions. Even in the absence of fatty acids and Ca2+ HlyA is an amphipathic protein, with a tendency to self-aggregation. However, Ca(2+)-binding appears to expose hydrophobic patches on the protein surface, facilitating both self-aggregation and irreversible insertion into membranes. The protein may somehow bind membranes in the absence of divalent cations, but only when Ca2+ (or Sr2+, or Ba2+) is bound to the toxin in aqueous suspensions, i.e., prior to its interaction with bilayers, can alpha-hemolysin bind irreversibly model or cell membranes in such a way that the integrity of the membrane barrier is lost, and cell or vesicle leakage ensues. Leakage is not due to the formation of proteinaceous pores, but rather to the transient disruption of the bilayer, due to the protein insertion into the outer membrane monolayer, and subsequent perturbations in the bilayer lateral tension. Protein or glycoprotein receptors for alpha-hemolysin may exist on the cell surface, but the toxin is also active on pure lipid bilayers.
α-溶血素最初作为一种含有1024个氨基酸的多肽被合成，随后在细胞内通过特定的脂肪酰化作用被激活。第二步激活过程发生在细胞外介质中，通过钙离子的结合来实现。即使在没有脂肪酸和钙离子的情况下，HlyA也是一种两亲性蛋白质，有自我聚集的倾向。然而，钙离子的结合似乎会使蛋白质表面暴露出疏水区域，这有利于自我聚集以及不可逆地插入细胞膜。在没有二价阳离子的情况下，该蛋白质可能会以某种方式与膜结合，但只有当钙离子（或锶离子，或钡离子）在水悬浮液中与毒素结合时，即在其与双层膜相互作用之前，α-溶血素才能以一种导致膜屏障完整性丧失、进而引起细胞或囊泡泄漏的方式不可逆地结合模型膜或细胞膜。泄漏不是由于蛋白质孔道的形成，而是由于蛋白质插入外膜单层导致双层膜的短暂破坏，以及随后双层膜侧向张力的扰动。α-溶血素的蛋白质或糖蛋白受体可能存在于细胞表面，但该毒素在纯脂质双层膜上也具有活性。
