li-moleculardetails-2018.pdf (2.08 MB)
Molecular details on the intermediate states of melittin action on a cell membrane
journal contribution
posted on 2018-11-01, 00:00 authored by Jiaojiao Liu, Shufeng Xiao, Jingliang LiJingliang Li, Bing Yuan, Kai Yang, Yuqiang MaAntimicrobial peptides (AMPs) provide a promising solution to the serious threat of multidrug-resistant bacteria or superbugs to public healthcare, due to their unique disruption to bacterial membrane such as perforation. Unfortunately, the underlying action mechanism of AMPs, especially the possible transition between the membrane binding and perforation states of peptides (i.e., the classical two-state model), is still largely unknown. Herein, by combining experimental techniques with pertinent membrane models and molecular dynamic (MD) simulations, new insights into the intermediate states of the AMP melittin-membrane interaction process are obtained. Specifically, it is demonstrated that, after the initial binding, the accumulated melittin on the bilayer triggers vigorous fluctuation of the membrane and even extracts some lipid molecules exclusively from the deformed outer leaflet of the bilayer. Such a distinctive mass removal manner and the resultant local asymmetry in lipid number between the two leaflets change the mechanical status of the membrane and in turn reduce the free energy barrier for the melittin insertion. Finally, the formation of the transmembrane pores is facilitated significantly. These findings provide new insights into the complicated antimicrobial mechanisms of AMPs.
History
Journal
Biochimica et Biophysica Acta - BiomembranesVolume
1860Issue
11Pagination
2234 - 2241Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
Link to full text
ISSN
0005-2736eISSN
1879-2642Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, ElsevierUsage metrics
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No categories selectedKeywords
Antimicrobial peptideCell membraneMelittinMolecular dynamic simulationsPerforation mechanismScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiophysicsQUARTZ-CRYSTAL MICROBALANCESUPPORTED LIPID-BILAYERSANTIMICROBIAL PEPTIDESPHOSPHOLIPID-MEMBRANESFORCE-FIELDSIMULATIONSMODELPORESSUBSEQUENTDEPOSITION
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