The cathelicidins--structure, function and evolution.
The cathelicidin family of host defense peptides includes a group of cationic and usually amphipathic peptides that display a variety of activities related to host defense functions, among which the most acknowledged is a direct antimicrobial activity against various microbial pathogens. All members of this family are synthesized as precursors characterized by an N-terminal cathelin-like domain which is relatively well conserved also in evolutionary distant vertebrates. By contrast, the C-terminal region, which carries the active peptide, appears to be a focus for genetic mechanisms that have selectively generated a considerable sequence diversity. This process is particularly striking in Cetartiodactyls, where repeated gene duplication events and subsequent divergence have produced an array of distinct family members. The corresponding mature cathelicidin peptides are considerably diverse in length, amino acid sequence and structure, variously adopting alpha-helical, elongated or beta-hairpin conformations. The diverse nature of these peptides may account for distinct functions and for a diverse spectrum of activity and/or antimicrobial potency.