Abstract
ABSTRACT
Antimicrobial peptides (AMPs) have long been ascribed the ability to form pores. These structures, some observed, others inferred, vary in their mechanisms of action, though most are associated with lysis. Here, we show that an AMP derived from a truncated staphylococcal δ‐toxin can form functional pores that do not cause rapid lysis but, instead, we suggest that they act as self‐transport systems. Specifically, a 17‐amino acid AMP named STIP3‐1 was observed to oligomerize and form a unique supramolecular helical assembly with an ∼14 Å pore. Substitutions to the STIP3‐1 peptide abolished our ability to detect pore formation in model membranes and prevented peptide accumulation in
Staphylococcus aureus
. In the case of G3A and G3Aib variants, the substitutions resulted in stabilization of antiparallel 4‐helix bundles rather than a nanotubular assembly characterized by a two‐ring structure formed by repeating trimers. MD simulations suggest that Gly may impart versatility in STIP3‐1 phospholipid binding. Our observation of this remarkable STIP3‐1 structure expands how we can approach mechanistic and translational studies of AMPs.