Abstract
Antimicrobial peptides (AMPs) are a diverse group of membrane-active peptides which play a crucial role as mediators of the primary host defense against microbial invasion. Many AMPs are found to be fully or partially disordered in solution and to acquire secondary structure upon interaction with a lipid membrane. Here, we report molecular dynamics simulations studies on the solution behaviour of a specific AMP, bombinin H2. We show that in monomeric form in water solution the peptide is somewhat disordered and preferably adopts a helix-loop-helix conformation. However, when more than a single monomer is placed in the solution, the peptides self-associate in aggregates. Within the aggregate, the peptides provide each other with an amphipathic environment that mimics the water–membrane interface, which allows them to adopt a single-helix structure. We hypothesise that this is the mechanism by which bombinin H2 and, possibly, other small linear AMPs reach the target membrane in a functional folded state and are able to effectively exert their antimicrobial action on it.
Highlights
Antimicrobial peptides (AMPs) are a crucial part of the nonspecific innate immunity of all eukaryotes to microbial invasion [1,2,3]
AMPs are generally membrane active peptides that interact with target membranes and can cause cell death through various mechanisms [1,4,5]: they can disturb the membrane by inducing thinning, altering its curvature or fluidity, modifying the transmembrane electrochemical gradient, and inducing pore formation [5,6]
We first focus on the dynamics of an isolated bombinin H2 monomer in water solution
Summary
Antimicrobial peptides (AMPs) are a crucial part of the nonspecific innate immunity of all eukaryotes to microbial invasion [1,2,3]. They are a diverse group of compounds, displaying various types of structures, including α-helices, β-sheets or cyclic structures. AMP aggregation in solution and in the absence of a membrane is not well studied, while this certainly is the first stage of their activity pathway whose significance is that way largely underestimated. In a very recent paper [25], the authors demonstrated that was α-helical structure necessary for the antimicrobial action of a specific AMP—halictine-1—and the “mechanism of the peptide mode of action probably involves formation of peptide assemblies (possibly membrane pores), which disrupt bacterial membrane and, allow membrane penetration”
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