Dermcidin

DCD
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
Aliases DCD, AIDD, DCD-1, DSEP, HCAP, PIF, dermcidin
External IDs OMIM: 606634 HomoloGene: 89039 GeneCards: DCD
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

117159

n/a

Ensembl

ENSG00000161634

n/a

UniProt

P81605

n/a

RefSeq (mRNA)

NM_053283
NM_001300854

n/a

RefSeq (protein)

NP_001287783.1
NP_444513.1

n/a

Location (UCSC) Chr 12: 54.64 – 54.65 Mb n/a
PubMed search [1] n/a
Wikidata
View/Edit Human

Dermcidin, also known as proteolysis-inducing factor (PIF), is a protein that in humans is encoded by the DCD gene.[2][3] It is an anti-microbial peptide[3] secreted by human eccrine sweat glands onto the skin as a part of the innate host defense of the immune system. It is also involved in proteolysis.[3]

Function

Dermcidin is a secreted protein that is subsequently processed into mature peptides of distinct biological activities. The C-terminal peptide is constitutively expressed in sweat and has antibacterial and antifungal activities. The N-terminal peptide, also known as diffusible survival evasion peptide, promotes neural cell survival under conditions of severe oxidative stress. A glycosylated form of the N-terminal peptide may be associated with cachexia (muscle wasting) in cancer patients.[3]

      Survival evasion peptide                            Antimicrobial peptide

YDPEAASAPGSGNPCHEASAAQKENAGEDPGLARQAPKPRKQRSSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL

The C-termial precursor DCD-1L is a 48 residue peptide that shows partial helicity in solution, as evidenced by the determination of its solution structure by NMR and CD-spectroscopy. The full length precursor is processed by undetermined proteases present in human sweat, to form several shorter peptides that show variable antimicrobial activity, named according to their C-terminal triplet of amino acids and their resiude length. One such active peptide is SSL25, which shows a 2-fold increase in activity against E.coli compared to DCD-1L.[4]

DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
DCD-1  SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV
SSL25  SSLLEKGLDGAKKAVGGLGKLGKDA

Mechanism

The crystal structure of dermcidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding.[5] This is observed to form a tilted channel in membranes under computational examination by molecular dynamics simulations, and one suggested mechanism of antimicrobial action inferred from this observation is by ion gradient decoupling across biological membranes. This is supported by concurrent observations in experimental studies of a voltage dependent depolarization of lipid bilayers.

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C (Nov 2001). "Dermicidin: a novel human antibiotic peptide secreted by sweat glands". Nat Immunol. 2 (12): 1133–7. doi:10.1038/ni732. PMID 11694882.
  3. 1 2 3 4 "Entrez Gene: DCD dermcidin".
  4. ↑ Baechle D, Flad T, Cansier A, et al. (2006). "Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L.". J. Biol. Chem. 281 (9): 5406–15. doi:10.1074/jbc.M504670200. PMID 16354654.
  5. ↑ PDB: 2YMK​Song, Chen; Weichbrodt, Conrad; Salnikov, Evgeniy S; Dynowski, Marek; Forsberg, Björn O; Bechinger, Burkhard; Steinem, Claudia; de Groot, Bert L; Zachariae, Ulrich; Zeth, Kornelius (Feb 2013). "Crystal structure and functional mechanism of a human antimicrobial membrane channel". PNAS. 110 (12): 4586–91. doi:10.1073/pnas.1214739110. PMID 23426625.

Further reading

External links

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