Datensatz

Zusammenfassung

Dermcidin (DCD) is one kind of antimicrobial peptides (AMPs), which is secreted into human sweat and protects human body against Gram-negative and -positive bacteria. Like most of the other AMPs, it carries great potential as new antibiotic. However, the functional mechanism of DCD and most of the AMPs is still elusive. One of the hypothesis of their function mechanisms involves their oligomerization and pore formation in bacterial membranes. Indeed, we have recently obtained the first crystal structure of the DCD oligomer, which represents a well-defined channel structure composed of six DCD monomers. Molecular dynamics (MD) simulations have been carried out on this novel channel structure, using the newly established “computational electrophysiology” method. We found that, the DCD hexameric channel structure is stable when embedded in the model membranes composed of POPE/POPG (3:1). This channel acts as a very efficient water permeation channel, as well as an ion channel with a conductance around 60 pS. Furthermore, it takes a tilted orientation around 20-30 degrees relative to the membrane surface normal to reduce the hydrophobic mismatch, due to its ∼8-nm length which is twice of the membrane thickness. Interestingly, the ions enter and exit the channel from its side windows rather than from the ends of the channel, thus forming a very unique ion permeation path. These findings bear direct significance for the functional mechanisms of DCD and the AMP family on bacterial membranes.