Dermcidin

DCD
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2YMK, 2KSG
Identifiers
Aliases	DCD, AIDD, DCD-1, DSEP, HCAP, PIF, dermcidin
External IDs	OMIM: 606634 HomoloGene: 89039 GeneCards: DCD
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.2 Start 54,644,591 bp[1] End 54,648,493 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptidase activity • protein binding • hydrolase activity • RNA binding Cellular component • extracellular exosome • extracellular matrix • extracellular region • extracellular space Biological process • defense response to bacterium • proteolysis • antimicrobial humoral response • antimicrobial humoral immune response mediated by antimicrobial peptide • killing of cells of other organism • defense response to fungus Sources:Amigo / QuickGO
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 NP_444513	n/a
Location (UCSC)	Chr 12: 54.64 – 54.65 Mb	n/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

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 resiude 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

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

Further reading

External links

• dermicidins at the US National Library of Medicine Medical Subject Headings (MeSH)