Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília-DF, Brazil.
Physical Chemistry and Soft Matter, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
Sci Rep. 2018 Jul 24;8(1):11127. doi: 10.1038/s41598-018-29444-0.
In order to study how acidic pro-peptides inhibit the antimicrobial activity of antimicrobial peptides, we introduce a simple model system, consisting of a 19 amino-acid long antimicrobial peptide, and an N-terminally attached, 10 amino-acid long acidic model pro-peptide. The antimicrobial peptide is a fragment of the crotalicidin peptide, a member of the cathelidin family, from rattlesnake venom. The model pro-peptide is a deca (glutamic acid). Attachment of the model pro-peptide only leads to a moderately large reduction in the binding to- and induced leakage of model liposomes, while the antimicrobial activity of the crotalicidin fragment is completely inhibited by attaching the model pro-peptide. Attaching the pro-peptide induces a conformational change to a more helical conformation, while there are no signs of intra- or intermolecular peptide complexation. We conclude that inhibition of antimicrobial activity by the model pro-peptide might be related to a conformational change induced by the pro-peptide domain, and that additional effects beyond induced changes in membrane activity must also be involved.
为了研究酸性前肽如何抑制抗菌肽的抗菌活性，我们引入了一个简单的模型系统，该系统由 19 个氨基酸长的抗菌肽和一个 N 端连接的 10 个氨基酸长的酸性模型前肽组成。抗菌肽是来自响尾蛇毒液的一种 cathelidin 家族的 crotalicidin 肽的片段。模型前肽是一个 deca（谷氨酸）。模型前肽的附着只会导致对模型脂质体的结合和诱导泄漏的适度降低，而附着模型前肽会完全抑制 crotalicidin 片段的抗菌活性。附着前肽诱导构象向更螺旋的构象变化，而没有迹象表明存在分子内或分子间肽复合物。我们得出结论，模型前肽对抗菌活性的抑制可能与前肽结构域诱导的构象变化有关，并且必须涉及除诱导的膜活性变化之外的其他影响。
