An ancestral host defence peptide within human ?-defensin 3 recapitulates the antibacterial and antiviral activity of the full-length molecule.

ABSTRACT: Host defence peptides (HDPs) are critical components of innate immunity. Despite their diversity, they share common features including a structural signature, designated "?-core motif". We reasoned that for each HDPs evolved from an ancestral ?-core, the latter should be the evolutionary starting point of the molecule, i.e. it should represent a structural scaffold for the modular construction of the full-length molecule, and possess biological properties. We explored the ?-core of human ?-defensin 3 (HBD3) and found that it: (a) is the folding nucleus of HBD3; (b) folds rapidly and is stable in human serum; (c) displays antibacterial activity; (d) binds to CD98, which mediates HBD3 internalization in eukaryotic cells; (e) exerts antiviral activity against human immunodeficiency virus and herpes simplex virus; and (f) is not toxic to human cells. These results demonstrate that the ?-core within HBD3 is the ancestral core of the full-length molecule and is a viable HDP per se, since it is endowed with the most important biological features of HBD3. Notably, the small, stable scaffold of the HBD3 ?-core can be exploited to design disease-specific antimicrobial agents.

SUBMITTER: Nigro E 

PROVIDER: S-EPMC4685272 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature