Dermcidin

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
DCD
Dermcidin-1L 2KSG.png
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesDCD, AIDD, DCD-1, DSEP, HCAP, PIF, dermcidin
External IDsOMIM: 606634 HomoloGene: 89039 GeneCards: DCD
Gene location (Human)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for DCD
Genomic location for DCD
Band12q13.2Start54,644,591 bp[1]
End54,648,493 bp[1]
RNA expression pattern
PBB GE DCD gnf1h01261 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_053283
NM_001300854

n/a

RefSeq (protein)

NP_001287783
NP_444513

n/a

Location (UCSC)Chr 12: 54.64 – 54.65 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Dermicidin, also known as proteolysis-inducing factor (PIF), is a protein that in humans is encoded by the DCD gene.[3][4] It is an anti-microbial peptide[4] 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.[4]

Function[edit]

Dermicidin 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.[4]

      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 residue length. One such active peptide is SSL25, which shows a 2-fold increase in activity against E.coli compared to DCD-1L.[5]

DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
DCD-1  SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV
SSL25  SSLLEKGLDGAKKAVGGLGKLGKDA

Mechanism[edit]

The crystal structure of dermicidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding.[6] 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[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000161634 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:".
  3. ^ 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.
  4. ^ a b c d "Entrez Gene: DCD dermicidin".
  5. ^ 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.
  6. ^ PDB: 2YMKSong, 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. PMC 3607029. PMID 23426625.

Further reading[edit]

External links[edit]