Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires, EAC 7149 CNRS Université Paris EST Créteil 61, Avenue du Général de Gaulle, 94010 Créteil Cedex, FRANCE.
Curr Pharm Biotechnol. 2011 Aug;12(8):1184-93. doi: 10.2174/138920111796117319.
Antimicrobial peptides (AMPs) produced by a wide variety of organisms are major actors of the host defense systems against invading pathogenic microorganisms. These peptides exhibit a broad spectrum of action against bacteria, yeasts, fungi, protozoa and viruses. It is widely believed that a large part of their antimicrobial effect derives from direct interactions with the lipid membrane surrounding the target cells, causing its permeabilization and cell lysis. However, the exact nature of these interactions is presently unclear. The skin of the amphibians has proved to be a remarkably rich storehouse of AMPs that encompass a wide variety of structural motifs. This natural AMP bank is used in combined approaches, based on biophysical and cellular biology methods, to elucidate how these peptides perturb the membrane and whether such membrane perturbations are related to the antimicrobial activity of these peptides. Here we review our current knowledge about the structure and the mechanism of action of the dermaseptin super-family, α-helical amphipathic AMPs isolated from the skin of frogs of the Phyllomedusa genus. Dermaseptins are genetically related, with a remarkable identity in signal sequences and acidic propieces of their preproforms but have clearly diverged to yield several families of microbicidal cationic peptides that are structurally distinct. Particularly, we focused on the orthologous peptides dermaseptin S and B of which the shortening from the carboxy terminal extremity causes a drastic change in their membrane disruption activity. These peptides could be good models to study the membrane-peptide interactions discussed in this review.
抗菌肽 (AMPs) 由各种生物体产生，是宿主防御系统对抗入侵的致病微生物的主要因子。这些肽对细菌、酵母、真菌、原生动物和病毒表现出广谱的作用。人们普遍认为，它们的大部分抗菌作用源于与靶细胞周围的脂质膜的直接相互作用，导致其通透性和细胞裂解。然而，这些相互作用的确切性质目前尚不清楚。两栖动物的皮肤被证明是 AMPs 的一个非常丰富的宝库，其中包含多种结构基序。这个天然的 AMP 库被用于结合生物物理和细胞生物学方法的综合方法，以阐明这些肽如何扰乱膜，以及这种膜扰动是否与这些肽的抗菌活性有关。在这里，我们回顾了我们目前对从 Phyllomedusa 属青蛙皮肤中分离出的 α-螺旋两亲性 AMPs 家族 dermaseptin 超家族的结构和作用机制的认识。Dermaseptins 在遗传上是相关的，其信号序列和前体的酸性前体具有显著的同一性，但已经明显分化，产生了几种结构不同的杀菌阳离子肽家族。特别是，我们集中研究了结构同源的 dermaseptin S 和 B，它们从羧基末端缩短会导致其膜破坏活性发生剧烈变化。这些肽可以作为研究本文讨论的膜-肽相互作用的良好模型。
