Dermcidin, an anionic antimicrobial peptide: influence of lipid charge, pH and Zn2+ on its interaction with a biomimetic membrane.

Article Details

Citation

Copy to clipboard

Becucci L, Valensin D, Innocenti M, Guidelli R

Dermcidin, an anionic antimicrobial peptide: influence of lipid charge, pH and Zn2+ on its interaction with a biomimetic membrane.

Soft Matter. 2014 Jan 28;10(4):616-26. doi: 10.1039/c3sm52400k.

PubMed ID

24652391 [ View in PubMed

]

Abstract

The mechanism of membrane permeabilization by dermcidin (DCD-1L), an antimicrobial peptide present in human sweat, was investigated at a mercury-supported monolayer of dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylserine (DOPS) and at a mercury-supported tethered bilayer lipid membrane (tBLM) consisting of a thiolipid (DPTL) with a DOPC or DOPS monolayer self-assembled on top of it. In an unbuffered solution of pH 5.4, DCD-1L is almost neutral and permeabilizes a DPTL/DOPS tBLM at transmembrane potentials, varphitrans, which are physiological. In a pH 7 buffer solution DCD-1L bears two negative charges and has no effect on a DPTL/DOPC tBLM, whereas it permeabilizes a DPTL/DOPS tBLM only outside the physiological varphitrans range; however, the presence of zinc ion induces DCD-1L to permeabilize the DPTL/DOPS tBLM at physiological varphitrans values. The effect of zinc ions suggests a DCD-1L conformation with its positive N-terminus embedded in the lipid bilayer and the negative C terminus floating on the membrane surface. This conformation can be stabilized by a zinc ion bridge between the His(38) residue of the C terminus and the carboxyl group of DOPS. Chronocoulometric potential jumps from varphitrans congruent with +160 mV to sufficiently negative values yield charge transients exhibiting a sigmoidal shape preceded by a relatively long "foot". This behavior is indicative of ion-channel formation characterized by disruption of DCD-1L clusters adsorbed on top of the lipid bilayer, incorporation of the resulting monomers and their aggregation into hydrophilic pores by a mechanism of nucleation and growth.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zinc chloride	Dermcidin	Protein	Humans	Unknown	Stabilization	Details
Zinc sulfate, unspecified form	Dermcidin	Protein	Humans	Unknown	Stabilization	Details