TCDB is operated by the Saier Lab Bioinformatics Group

1.C.108 The Pore-forming Dermcidin (Dermcidin) Family

Song et al. (2013) presented the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology and MD simulations of human dermcidin (DCD) (also called preproteolysin) in membranes. These studies revealed the antibiotic mechanism of this major human antimicrobial which suppresses Staphylococcus aureus growth on epidermal surfaces. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidated the unusual membrane permeation pathway for ions and showed adjustment of the pore to various membranes. These study unraveled the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at the atomic level (Song et al., 2013).

Bilayers composed of various lipids (DMPC, DPPC, and DSPC) with different thicknesses result in different orientations of the DCD oligomer; the thicker the bilayer, the less tilted the channel (Song et al. 2019). Cholesterol makes the bilayers more rigid and thicker, which also affects the orientation of the channel. The predicted conductance of the channel is related to its orientation in the lipid bilayer: the larger the tilt, the larger the conductance. Thus, thicker, cholesterol-rich membranes show lower conductance than that of thinner membranes (Song et al. 2019).

References associated with 1.C.108 family:

Song, C., B.L. de Groot, and M.S.P. Sansom. (2019). Lipid Bilayer Composition Influences the Activity of the Antimicrobial Peptide Dermcidin Channel. Biophys. J. 116: 1658-1666. 31010668
Song, C., C. Weichbrodt, E.S. Salnikov, M. Dynowski, B.O. Forsberg, B. Bechinger, C. Steinem, B.L. de Groot, U. Zachariae, and K. Zeth. (2013). Crystal structure and functional mechanism of a human antimicrobial membrane channel. Proc. Natl. Acad. Sci. USA 110: 4586-4591. 23426625
Zeth, K. and E. Sancho-Vaello. (2017). The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions. Front Chem 5: 86. 29164103