Self-Assembly of Linear, Natural Antimicrobial Peptides: An Evolutionary Perspective

Antimicrobial peptides are an ancient and innate system of host defence against a wide range of microbial assailants. Mechanistically, unstructured peptides undergo a secondary structure transition into amphipathic alpha-helices, upon contact with membrane surfaces. This leads to peptide binding and removal of the membrane components in a detergent-like manner or via self-organisation into trans-membrane pores (either barrel-stave or toroidal pore) thereby destroying the microbe. Self-assembly of antimicrobial peptides into oligomers and ultimately amyloid has been mostly examined in parallel, however recent findings link diseases, such as Alzheimer's disease as an aberrant activity of a protective neuropeptide with antimicrobial activity. These self-assembled oligomers can also interact with membranes. Here, we review those antimicrobial peptides reported to self-assemble into amyloid, where supported by structural evidence. We consider their membrane activities as antimicrobial peptides and present evidence of consistent self-assembly patterns across major evolutionary groups. Trends are apparent across these groups, supporting the mounting data that self-assembly of antimicrobial peptides into amyloid should be considered as synergistic to the antimicrobial peptide response.

Automated summary

Antimicrobial peptides are a crucial defense mechanism of hosts against microbial assailants. They undergo a structural transition upon contact with membrane surfaces, leading to the destruction of microbes through detergent-like binding or formation of trans-membrane pores. Recent findings also suggest a potential link between self-assembled antimicrobial peptides and diseases like Alzheimer's disease. This review highlights the importance of studying the self-assembly of antimicrobial peptides into amyloid and its synergistic effect with the antimicrobial peptide response.