Understanding membrane-active antimicrobial peptides.

IF 7.2 2区 生物学 Q1 BIOPHYSICS
Huey W Huang, Nicholas E Charron
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引用次数: 43

Abstract

Bacterial membranes represent an attractive target for the design of new antibiotics to combat widespread bacterial resistance to traditional inhibitor-based antibiotics. Understanding how antimicrobial peptides (AMPs) and other membrane-active agents attack membranes could facilitate the design of new, effective antimicrobials. AMPs, which are small, gene-encoded host defense proteins, offer a promising basis for the study of membrane-active antimicrobial agents. These peptides are cationic and amphipathic, spontaneously binding to bacterial membranes and inducing transmembrane permeability to small molecules. Yet there are often confusions surrounding the details of the molecular mechanisms of AMPs. Following the doctrine of structure-function relationship, AMPs are often viewed as the molecular scaffolding of pores in membranes. Instead we believe that the full mechanism of AMPs is understandable if we consider the interactions of AMPs with the whole membrane domain, where interactions induce structural transformations of the entire membrane, rather than forming localized molecular structures. We believe that it is necessary to consider the entire soft matter peptide-membrane system as it evolves through several distinct states. Accordingly, we have developed experimental techniques to investigate the state and structure of the membrane as a function of the bound peptide to lipid ratio, exactly as AMPs in solution progressively bind to the membrane and induce structural changes to the entire system. The results from these studies suggest that global interactions of AMPs with the membrane domain are of fundamental importance to understanding the antimicrobial mechanisms of AMPs.

了解膜活性抗菌肽。
细菌膜代表了一个有吸引力的目标,设计新的抗生素,以对抗广泛的细菌对传统的基于抑制剂的抗生素的耐药性。了解抗菌肽(AMPs)和其他膜活性物质如何攻击膜可以促进新的,有效的抗菌剂的设计。AMPs是一种小的、基因编码的宿主防御蛋白,为膜活性抗菌药物的研究提供了良好的基础。这些多肽是阳离子和两亲性的,可以自发地结合到细菌膜上,并诱导小分子的跨膜渗透性。然而,围绕amp分子机制的细节,人们常常感到困惑。根据结构-功能关系的原则,amp通常被视为膜上毛孔的分子支架。相反,我们认为,如果我们考虑amp与整个膜结构域的相互作用,amp的完整机制是可以理解的,其中相互作用诱导整个膜的结构转变,而不是形成局部的分子结构。我们认为有必要考虑整个软物质肽-膜系统,因为它经过几个不同的状态演变。因此,我们开发了实验技术来研究膜的状态和结构作为结合肽与脂质比率的函数,正如溶液中的amp逐渐结合到膜上并诱导整个系统的结构变化一样。这些研究结果表明,抗菌肽与膜结构域的整体相互作用对理解抗菌肽的抗菌机制具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Quarterly Reviews of Biophysics
Quarterly Reviews of Biophysics 生物-生物物理
CiteScore
12.90
自引率
1.60%
发文量
16
期刊介绍: Quarterly Reviews of Biophysics covers the field of experimental and computational biophysics. Experimental biophysics span across different physics-based measurements such as optical microscopy, super-resolution imaging, electron microscopy, X-ray and neutron diffraction, spectroscopy, calorimetry, thermodynamics and their integrated uses. Computational biophysics includes theory, simulations, bioinformatics and system analysis. These biophysical methodologies are used to discover the structure, function and physiology of biological systems in varying complexities from cells, organelles, membranes, protein-nucleic acid complexes, molecular machines to molecules. The majority of reviews published are invited from authors who have made significant contributions to the field, who give critical, readable and sometimes controversial accounts of recent progress and problems in their specialty. The journal has long-standing, worldwide reputation, demonstrated by its high ranking in the ISI Science Citation Index, as a forum for general and specialized communication between biophysicists working in different areas. Thematic issues are occasionally published.
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