AMPs In Action

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Science  08 Mar 2013:
Vol. 339, Issue 6124, pp. 1127
DOI: 10.1126/science.339.6124.1127-a

Antimicrobial peptides (AMPs) provide an important first-line defense against bacteria and fungi in multicellular organisms. They do so by targeting the microbial cell membrane, but their precise mechanisms of action are not well understood. Song et al. used a combination of x-ray crystallography, electrophysiology, and molecular dynamics simulations to better understand the mechanism of one such AMP: dermcidin (DCD). DCD is secreted into human sweat and found on the skin. It is active against a range of bacteria, including methicillin-resistant Staphylococcus aureus and Mycobacterium tuberculosis. The authors' analysis revealed that DCD forms a hexameric barrel-like channel of elongated α helices in bacterial membranes. Stabilization of the channel required the presence of zinc. The channel formed was highly permeable to water and ions and so was a major membrane disruptor. This ability to disrupt the transmembrane potential of bacterial cell membranes can lead to rapid cell death and thus provide protective antimicrobial activity to the host.

Proc. Natl. Acad. Sci. U.S.A. 110, 10.1073/pnas.1214739110 (2013).

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