Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles.
Dermcidin is a human antibiotic peptide that is secreted by the sweat glands and has no homology to other known antimicrobial peptides. As an initial step toward understanding dermcidin's mode of action at bacterial membranes, we used homonuclear and heteronuclear NMR to determine the conformation of the peptide in 50% trifluoroethanol solution. We found that dermcidin adopts a flexible amphipathic alpha-helical structure with a helix-hinge-helix motif, which is a common molecular fold among antimicrobial peptides. Spin-down assays of dermcidin and several related peptides revealed that the affinity with which dermcidin binds to bacterial-mimetic membranes is primarily dependent on its amphipathic alpha-helical structure and its length (>30 residues); its negative net charge and acidic pI have little effect on binding. These findings suggest that the mode of action of dermcidin is similar to that of other membrane-targeting antimicrobial peptides, though the details of its antimicrobial action remain to be determined.
Jung
Hyun Ho
HH
Department of Life Science, Gwangju Institute of Science and Technology, Korea.
Yang
Sung-Tae
ST
Sim
Ji-Yeong
JY
Lee
Seungkyu
S
Lee
Ju Yeon
JY
Kim
Ha Hyung
HH
Shin
Song Yub
SY
Kim
Jae Il
JI
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry
D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010743:Phospholipids; D012996:Solutions; C442243:dermcidin