Molecular details on the intermediate states of melittin action on a cell membrane

Publication date: Available online 10 September 2018Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Jiaojiao Liu, Shufeng Xiao, Jingliang Li, Bing Yuan, Kai Yang, Yuqiang MaAbstractAntimicrobial 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 mec...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research