Open AccessInvestigating Antimicrobial Peptide–Membrane Interactions Using Fast Photochemical Oxidation of Peptides in Nanodiscs
Author(s) -
Deseree J. Reid,
James G. Rohrbough,
Marius Kostelic,
Michael T. Marty
Publication year - 2021
Publication title -
journal of the american society for mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 127
eISSN - 1879-1123
pISSN - 1044-0305
DOI - 10.1021/jasms.1c00252
Subject(s) - chemistry , antimicrobial peptides , lipid bilayer , peptide , lipid a , biophysics , liposome , membrane , lipid ii , biochemistry , combinatorial chemistry , bacteria , biosynthesis , biology , genetics , enzyme
Antimicrobial peptides (AMPs) are an important part of the innate immune system and demonstrate promising applications in the fight against antibiotic-resistant infections due to their unique mechanism of targeting bacterial membranes. However, it is challenging to study the interactions of these peptides within lipid bilayers, making it difficult to understand their mechanisms of toxicity and selectivity. Here, we used fast photochemical oxidation of peptides, an irreversible footprinting technique that labels solvent accessible residues, and native charge detection-mass spectrometry to study AMP-lipid interactions with different lipid bilayer nanodiscs. We observed differences in the oxidation of two peptides, indolicidin and LL-37, in three distinct lipid environments, which reveal their affinity for lipid bilayers. Our findings suggest that indolicidin interacts with lipid head groups via a simple charge-driven mechanism, but LL-37 is more specific for Escherichia coli nanodiscs. These results provide complementary information on the potential modes of action and lipid selectivity of AMPs.