Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms

► Not all histone-derived antimicrobial peptides (HDAPs) use the same mechanism. ► DesHDAP1 shows proline-dependent translocation, analogous to buforin II. ► In DesHDAP3, proline to alanine mutation increases membrane lysis and potency. ► Proline promotes membrane translocation in some antimicrobial peptides. ► Amphipathicity, not α-helicity, determines lytic abilities of proline mutants.