The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment

Human beta -defensin-2 (HBD-2) is a member of the defensin family of antimi crobial peptides. HBD-2 was first isolated from inflamed skin where it is p osited to participate in the killing of invasive bacteria and in the recrui tment of cells of the adaptive immune response. Static light scattering and two-dimensional proton nuclear magnetic resonance spectroscopy have been u sed to assess the physical state and structure of HBD-2 in solution. At con centrations of less than or equal to2.4 mM, HBD-2 is monomeric. The structu re is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta -sheet with strands 2 and 3 in a beta -hairpin conformat ion. A beta -bulge in the second strand occurs at Gly28, a position conserv ed in the entire defensin family. In solution, HBD-2 exhibits an alpha -hel ical segment near the N-terminus that has not been previously ascribed to s olution structures of alpha -defensins or to the beta -defensin BNBD-12. Th is novel structural element may be a factor contributing to the specific mi crobicidal or chemokine-like properties of HBD-2.