Structural basis for the bacterial membrane insertion of dermcidin peptide, DCD-1L
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Abstract
© 2017 The Author(s). Human dermcidin (DCD) is an antimicrobial peptide secreted constitutively by sweat glands. The anionic derivative, DCD-1L, comprises of the N-terminal 47 residues of DCD and one additional leucine residue. A previous NMR structure of DCD-1L in 50% TFE showed a partial helical conformation, and its crystal structure in the presence of Zn2+ outlined a hexameric linear α-helical bundle. Three different models to describe membrane insertion were proposed but no conclusion was drawn. In the current study, the NMR structure of DCD-1L in SDS micelles showed an "L-shaped" molecule with three fully formed α-helices connected by flexible turns. Formation of these helices in DCD-1L in the presence of POPG vesicles suggests that the acidic C-terminal region of DCD-1L can suppress the binding of DCD-1L to POPG vesicles at basic but not acidic pH. Mutation of charged residues on the N-terminal and C-terminal regions of DCD-1L cause differences in POPG binding, suggesting distinct functional roles for these two regions. Charged residues from these two regions are also found to differentially affect Zn2+ coordination and aggregation of DCD-1L in the absence or presence of SDS, as monitored by 1D NMR. Our data agrees with one of the three models proposed.
Keywords
Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ANTIMICROBIAL PEPTIDE, C-13/N-15-ENRICHED PROTEINS, NMR-SPECTROSCOPY, ECCRINE SWEAT, RESONANCES, ASSIGNMENT, BACKBONE, SKIN, MECHANISM, GLANDS
Source Title
SCIENTIFIC REPORTS
Publisher
NATURE PUBLISHING GROUP
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Date
2017-10-24
DOI
10.1038/s41598-017-13600-z
Type
Article