Effect of helical kink in antimicrobial peptides on membrane pore formation

Antimicrobial peptides (AMPs) can kill pathogens via the formation of permeable membrane pores. However, matching peptide properties with their ability to form pores remains elusive. In particular, the proline/glycine kink in helical AMPs was reported to both increase and decrease antimicrobial activity. We used computer simulations and fluorescence leakage experiments to show that a kink in helices affects the formation of membrane pores by stabilizing toroidal pores but disrupting barrel-stave pores. The precise position of the proline/glycine kink in the sequence further controls the formation of specific toroidal pore structure: U- or hourglass-shaped. Moreover, we demonstrate that two helical peptides can form a stable kink-like connection with similar behavior as one long helical peptide with kink. The provided molecular-level insight can be utilized for rational design or modification of antibacterial peptides or toxins to alter their ability to form membrane pores.