Abstract
The antimicrobial peptide magainin 2 (M2) interacts with and induces structural damage in bacterial cell membranes. Although extensive biophysical studies have revealed the interaction mechanism between M2 and membranes, the mechanism of membrane-mediated oligomerization of M2 is controversial. Here, we measured the synchrotron-radiation circular dichroism and linear dichroism (LD) spectra of M2 in dipalmitoyl-phosphatidylglycerol lipid membranes in lipid-to-peptide (L/P) molar ratios from 0–26 to characterize the conformation and orientation of M2 on the membrane. The results showed that M2 changed from random coil to α-helix structures via an intermediate state with increasing L/P ratio. Singular value decomposition analysis supported the presence of the intermediate state, and global fitting analysis revealed that M2 monomers with an α-helix structure assembled and transformed into M2 oligomers with a β-strand-rich structure in the intermediate state. In addition, LD spectra showed the presence of β-strand structures in the intermediate state, disclosing their orientations on the membrane surface. Furthermore, fluorescence spectroscopy showed that the formation of β-strand oligomers destabilized the membrane structure and induced the leakage of calcein molecules entrapped in the membrane. These results suggest that the formation of β-strand oligomers of M2 plays a crucial role in the disruption of the cell membrane.
Highlights
Antimicrobial resistance (AMR) is one of the most serious global threats to healthcare and agriculture
We found two iso-dichroic points around 200 and 210 nm during the spectral change, implying that magainin 2 (M2) formed a helical conformation in the DPPG membranes through an intermediate state
Our findings demonstrate that the oligomeric β-strand structure of M2 in membranes plays a crucial role in the disruption of the cell membrane
Summary
Antimicrobial resistance (AMR) is one of the most serious global threats to healthcare and agriculture. Antimicrobial peptides (AMPs) are a potential solution to this problem because they have broad-spectrum antibacterial, antifungal, and antiviral activities and it is difficult for microorganisms to acquire AMR against them [2,3]. The antimicrobial mechanism of AMP is different from that of conventional antibiotics; antibiotics inhibit the synthesis of bacterial components, whereas AMPs interact with bacterial cell membranes and directly cause damage to the membrane structure [2,4]. Further understanding of the interaction mechanism between AMP and membranes at the molecular level are necessary to gain new insights into the design strategy of effective AMP [8]
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