Demel R A, Peelen T, Siezen R J, De Kruijff B, Kuipers O P
Department of Biochemistry of Membranes, Utrecht University, The Netherlands.
Eur J Biochem. 1996 Jan 15;235(1-2):267-74. doi: 10.1111/j.1432-1033.1996.00267.x.
Monomolecular layers of lipids at the air/water interface have been used as a model membrane to study membrane interactions of the lantibiotic nisin. The natural lantibiotics nisin A and nisin Z proved to have a high affinity for the anionic lipids phosphatidylglycerol and bis(phosphatidyl)glycerol (cardiolipin). The interaction with zwitterionic phopholipids or neutral lipids is very low at surface pressures higher than 32 mN/m. Nisin, nisin mutants and lacticin 481 show a remarkable correlation between anti-microbial activity and anionic lipid interaction. The results indicate that primarily the N-terminal part (residues 1-22) penetrates into the lipid phase. Reduction of the flexibility at positions 20-21 has a negative effect on monolayer interaction and activity. The C-terminal part is probably responsible for ionic interactions of nisin in monomeric or oligomeric form with anionic lipids. In mixtures of anionic and zwitterionic lipids maximal interactions are found at approximately 70 mol/100 mol anionic lipid. Gram-positive bacteria, which form the main target for nisin, are characterized by a high content of anionic lipids in the membrane. Monolayers formed of lipid extracts of bacteria sensitive to nisin were more strongly penetrated than those of bacteria relatively insensitive to nisin.
空气/水界面的脂质单分子层已被用作模型膜来研究羊毛硫抗生素乳链菌肽的膜相互作用。天然羊毛硫抗生素乳链菌肽A和乳链菌肽Z被证明对阴离子脂质磷脂酰甘油和双（磷脂酰）甘油（心磷脂）具有高亲和力。在高于32 mN/m的表面压力下，与两性离子磷脂或中性脂质的相互作用非常低。乳链菌肽、乳链菌肽突变体和乳酸乳球菌素481在抗菌活性和阴离子脂质相互作用之间呈现出显著的相关性。结果表明，主要是N端部分（第1 - 22位残基）穿透到脂质相中。第20 - 21位的柔韧性降低对单分子层相互作用和活性有负面影响。C端部分可能负责单体或寡聚形式的乳链菌肽与阴离子脂质的离子相互作用。在阴离子和两性离子脂质的混合物中，在约70 mol/100 mol阴离子脂质时发现最大相互作用。作为乳链菌肽主要作用靶点的革兰氏阳性菌，其细胞膜中阴离子脂质含量高。由对乳链菌肽敏感的细菌的脂质提取物形成的单分子层比那些对乳链菌肽相对不敏感的细菌的单分子层更易被穿透。
