Membrane interaction of chrysophsin-1, a histidine-rich antimicrobial peptide from red sea bream
Membrane interaction of chrysophsin-1, a histidine-rich antimicrobial peptide from red sea bream
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DOI：
10.1021/bi701344m
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发表时间：
2007-12-25
期刊：
影响因子：
2.9
通讯作者：
Bechinger, Burkhard
中科院分区：
文献类型：
--
作者：
Mason, A. James;Bertani, Philippe;Bechinger, Burkhard
α-螺旋抗菌肽-1是由真鲷鳃细胞产生的两亲性α-螺旋抗菌肽。该肽对革兰氏阳性和革兰氏阴性细菌都具有广泛的活性，但比其他抗微生物肽如爪蟾抗菌肽更具溶血性。在这里，我们探讨膜相互作用的chrysophsin-1，并确定其毒性，在体外，人肺成纤维细胞获得其抗菌活性的机制，并了解不寻常的C-末端RRRH序列的作用。在中间肽浓度下，固态NMR方法揭示，chrysophsin-1平行于膜表面排列，并且混合模型膜中的脂质酰基链不稳定，从而与其中透化是瞬时膜破坏的效果的模型一致。显示C-末端RRRH序列对将肽插入具有不同脂质组成的膜中具有很大的影响，并且发现其对于孔形成和肽对成纤维细胞的毒性至关重要。生物物理数据和基于细胞的测定的组合表明，可能的机制涉及的抗生素和毒性活性的金霉素。
Chrysophsin-1 is an amphipathic a-helical antimicrobial peptide produced in the gill cells of red sea bream. The peptide has broad range activity against both Gram-positive and Gram-negative bacteria but is more hemolytic than other antimicrobial peptides such as magainin. Here we explore the membrane interaction of chrysophsin-1 and determine its toxicity, in vitro, for human lung fibroblasts to obtain a mechanism for its antimicrobial activity and to understand the role of the unusual C-terminal RRRH sequence. At intermediate peptide concentrations, solid-state NMR methods reveal that chrysophsin-1 is aligned parallel to the membrane surface and the lipid acyl chains in mixed model membranes are destabilized, thereby being in agreement with models where permeabilization is an effect of transient membrane disruption. The C-terminal RRRH sequence was shown to have a large effect on the insertion of the peptide into membranes with differing lipid compositions and was found to be crucial for pore formation and toxicity of the peptide to fibroblasts. The combination of biophysical data and cell-based assays suggests likely mechanisms involved in both the antibiotic and toxic activity of chrysophsins.