Abstract:
Antimicrobial peptides (AMPs) play a key role in the external immunity of animals, offering an interesting model for studying the influence of the environment on the diversification and evolution of immune effectors. Alvinellacin (ALV), arenicin (ARE) and polaricin (POL, a novel AMP identified here), characterized from three marine worms inhabiting contrasted habitats (\'hot\' vents, temperate and polar respectively), possess a well conserved BRICHOS domain in their precursor molecule despite a profound amino acid and structural diversification of the C-terminal part containing the core peptide. Data not only showed that ARE, ALV and POL display an optimal bactericidal activity against the bacteria typical of the habitat where each worm species lives but also that this killing efficacy is optimal under the thermochemical conditions encountered by their producers in their environment. Moreover, the correlation between species habitat and the cysteine contents of POL, ARE and ALV led us to investigate the importance of disulfide bridges in their biological efficacy as a function of abiotic pressures (pH and temperature). The construction of variants using non-proteinogenic residues instead of cysteines (α-aminobutyric acid variants) leading to AMPs devoid of disulfide bridges, provided evidence that the disulfide pattern of the three AMPs allows for a better bactericidal activity and suggests an adaptive way to sustain the fluctuations of the worm\'s environment. This work shows that the external immune effectors exemplified here by BRICHOS AMPs are evolving under strong diversifying environmental pressures to be structurally shaped and more efficient/specific under the ecological niche of their producer.
摘要:
抗菌肽(AMPs)在动物的外部免疫中起着关键作用,为研究环境对免疫效应子的多样化和进化的影响提供了一个有趣的模型。,阿尔维纳沙星(ALV),白利素(ARE)和极霉素(POL,此处确定的新型AMP),以三种居住在对比栖息地的海洋蠕虫为特征(“热”通风口,分别为温带和极地),尽管含有核心肽的C末端部分具有深刻的氨基酸和结构多样化,但在它们的前体分子中具有非常保守的BRICHOS结构域。数据不仅表明,ALV和POL对每个蠕虫物种生活的栖息地的典型细菌表现出最佳的杀菌活性,而且这种杀灭功效在其生产者在其环境中遇到的热化学条件下是最佳的。此外,物种生境与POL的半胱氨酸含量之间的相关性,ARE和ALV使我们研究了二硫键在其生物功效中作为非生物压力(pH和温度)函数的重要性。使用非蛋白质残基代替半胱氨酸(α-氨基丁酸变体)的变体的构建导致缺乏二硫键的AMP,提供的证据表明,三种AMP的二硫化物模式允许更好的杀菌活性,并提出了一种适应性方法来维持蠕虫环境的波动。这项工作表明,以BRICHOSAMP为例的外部免疫效应物在强大的多样化环境压力下不断发展,在其生产者的生态位下在结构上形成并更有效/特异性。