Structuring and interactions of human beta-defensins 2 and 3 with model membranes

β-Defensins play an important role in both innate and adaptive immunity. Interaction with biological membranes appears to be a central theme in modulating these activities, leading to different consequences such as membrane lysis, translocation into the cytoplasm or transfer to a receptor. We have investigated the structuring of human β-defensins (hBD2 and hBD3) and rationally designed variants, in relation to their interactions with real and model membranes. Our results indicate that structural features, such as the helical N-terminal domains and oligomerisation at the membrane surface, may modulate the efficiency of membrane insertion and selectivity for microbial or host-cell membranes. We propose that both peptides interact with membranes as extended β-sheet platforms that present amphipathic helices for insertion into the lipid bilayer.