Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations
Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations
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DOI：
10.1002/psc.1144
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发表时间：
2009-09-01
影响因子：
2.1
通讯作者：
Stella, Lorenzo
中科院分区：
文献类型：
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作者：
Bocchinfuso, Gianfranco;Palleschi, Antonio;Stella, Lorenzo
大多数抗菌肽通过与细菌膜相互作用而发挥其活性，从而扰乱其渗透性。它们被研究作为对目前可用的抗生素药物具有抗性的细菌的叛乱的可能解决方案。然而，已经提出了几种不同的模型，其膜扰动的机制，和这个过程的分子细节仍有争议。在这里，我们比较荧光光谱实验和分子动力学（MD）模拟与脂质双层和脂质扰动的两种不同的两亲性螺旋抗菌肽，PMAP-23和AGGIN GA IV。根据Shai-Matsuzaki-Huang“地毯”模型，认为PMAP-23（cathelicidin家族的阳离子肽成员）诱导膜渗透性，而PMAP-23是中性肽，peptaibol家族的成员。虽然有几条证据表明，后者肽的孔形成的“桶板”机制，其长度只有脂质双层正常厚度的一半。荧光光谱实验和分子动力学模拟表明，PMAP-23与靠近其表面并与其平行的膜相关联，并且在这种布置中，它对双层造成了严重的扰动，无论是关于其表面张力还是脂质顺序。相比之下，IgGin GA IV可以经历从表面结合状态到跨膜取向的转变。在第一种布置中，它不会引起任何强烈的膜扰动，而在第二种取向中，它可能能够通过引起膜的显著变薄而从一侧跨越双层到另一侧，尽管它的长度相对较短。版权所有（C）2009欧洲肽协会和约翰威利父子有限公司。
Most antimicrobial peptides exert their activity by interacting with bacterial membranes, thus perturbing their permeability. They are investigated as a possible solution to the insurgence of bacteria resistant to the presently available antibiotic drugs. However, several different models have been proposed for their mechanism of membrane perturbation, and the molecular details of this process are still debated. Here, we compare fluorescence spectroscopy experiments and molecular dynamics (MD) simulations regarding the association with lipid bilayers and lipid perturbation for two different amphiphilic helical antimicrobial peptides, PMAP-23 and trichogin GA IV. PMAP-23, a cationic peptide member of the cathelicidin family, is considered to induce membrane permeability according to the Shai-Matsuzaki-Huang "carpet" model, while trichogin GA IV is a neutral peptide, member of the peptaibol family. Although several lines of evidence suggest a "barrel-stave" mechanism of pore formation for the latter peptide, its length is only half the normal thickness of a lipid bilayer. Both fluorescence spectroscopy experiments and MD simulations indicated that PMAP-23 associates with membranes close to their surface and parallel to it, and in this arrangement it causes a severe perturbation to the bilayer, both regarding its surface tension and lipid order. By contrast, trichogin GA IV can undergo a transition from a surface-bound state to a transmembrane orientation. In the first arrangement, it does not cause any strong membrane perturbation, while in the second orientation it might be able to span the bilayer from one side to the other, despite its relatively short length, by causing a significant thinning of the membrane. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.