The Location of the Antimicrobial Peptide Maculatin 1.1 in Model Bacterial Membranes

• Published in: Frontiers in chemistry Vol. 8; p. 572
• Main Authors: Le Brun, Anton P, Zhu, Shiying, Sani, Marc-Antoine, Separovic, Frances
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.07.2020
• Subjects: antimicrobial peptide; bicelles; Chemistry; neutron reflectometry; paramagnetic relaxation enhancement; solid-state NMR; solution NMR; paramagnetic relaxation enhancement; solid-state NMR; bicelles; mode of action; neutron reflectometry; solution NMR; antimicrobial peptide; molecular dynamics
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2020.00572

Maculatin 1.1 (Mac1) is an antimicrobial peptide (AMP) from the skin secretions of Australian tree frogs. In this work, the interaction of Mac1 with anionic phospholipid bilayers was investigated by NMR, circular dichroism (CD) spectroscopy, neutron reflectometry (NR) and molecular dynamics (MD). In buffer, the peptide is unstructured but in the presence of anionic (DPC/LMPG) micelles or (DMPC/DMPG/DHPC) bicelles adopts a helical structure. Addition of the soluble paramagnetic agent gadolinium (Gd-DTPA) into the Mac1-DPC/LMPG micelle solution showed that the N-terminus is more exposed to the hydrophilic Gd-DTPA than the C-terminus in micelles. H and P solid-state NMR showed that Mac1 had a greater effect on the anionic lipid (DMPG). A deuterium labeled Mac1 used in NR experiments indicated that the AMP spanned across anionic (PC/PG) bilayers, which was compatible with MD simulations. Simulations also showed that Mac1 orientation remained transmembrane in bilayers and wrapped on the surface of the micelles regardless of the lipid or detergent charge. Thus, the peptide orientation appears to be more susceptible to curvature than charged surface. These results support the formation of transmembrane pores by Mac1 in model bacterial membranes.