title: Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat.
abstract: Dermcidin encodes the anionic amphiphilic peptide DCD-1L, which displays a broad spectrum of antimicrobial activity under conditions resembling those in human sweat. Here, we have investigated its mode of antimicrobial activity. We found that DCD-1L interacts preferentially with negatively charged bacterial phospholipids with a helix axis that is aligned flat on a lipid bilayer surface. Upon interaction with lipid bilayers DCD-1L forms oligomeric complexes that are stabilized by Zn(2+). DCD-1L is able to form ion channels in the bacterial membrane, and we propose that Zn(2+)-induced self-assembly of DCD-1L upon interaction with bacterial lipid bilayers is a prerequisite for ion channel formation. These data allow us for the first time to propose a molecular model for the antimicrobial mechanism of a naturally processed human anionic peptide that is active under the harsh conditions present in human sweat.
authors.affiliation: Department of Dermatology, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Paulmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnold
authors.forename: Dirk
authors.initials: D
authors.lastname: Linke
authors.forename: Suat
authors.initials: S
authors.lastname: Özdirekcan
authors.forename: Annika
authors.initials: A
authors.lastname: Kopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Ines
authors.initials: I
authors.lastname: Wanke
authors.forename: Verena J
authors.initials: VJ
authors.lastname: Schuenemann
authors.forename: Michael
authors.initials: M
authors.lastname: Habeck
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism; D013329:Structure-Activity Relationship; D013542:Sweat / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D010743:Phospholipids; C442243:dermcidin