Dermcidin: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: HTTP→HTTPS)
imported>Ira Leviton
m (Fixed a typo found with Wikipedia:Typo_Team/moss.)
 
Line 1: Line 1:
{{Infobox_gene}}
{{Infobox_gene}}
'''Dermcidin''', also known as '''proteolysis-inducing factor''' ('''PIF'''), is a [[protein]] that in humans is encoded by the ''DCD'' [[gene]].<ref name="pmid11694882">{{cite journal | vauthors = Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C | title = Dermicidin: a novel human antibiotic peptide secreted by sweat glands | journal = Nat Immunol | volume = 2 | issue = 12 | pages = 1133–7 |date=Nov 2001 | pmid = 11694882 | pmc =  | doi = 10.1038/ni732 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DCD dermcidin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=117159| accessdate = }}</ref> It is an [[anti-microbial]] [[peptide]]<ref name="entrez" /> secreted by human [[eccrine sweat gland]]s onto the skin as a part of the innate host defense of the immune system.  It is also involved in proteolysis.<ref name="entrez" />
'''Dermicidin''', also known as '''proteolysis-inducing factor''' ('''PIF'''), is a [[protein]] that in humans is encoded by the ''DCD'' [[gene]].<ref name="pmid11694882">{{cite journal | vauthors = Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C | title = Dermicidin: a novel human antibiotic peptide secreted by sweat glands | journal = Nat Immunol | volume = 2 | issue = 12 | pages = 1133–7 |date=Nov 2001 | pmid = 11694882 | pmc =  | doi = 10.1038/ni732 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DCD dermicidin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=117159| accessdate = }}</ref> It is an [[anti-microbial]] [[peptide]]<ref name="entrez" /> secreted by human [[eccrine sweat gland]]s onto the skin as a part of the innate host defense of the immune system.  It is also involved in proteolysis.<ref name="entrez" />


== Function ==
== 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.<ref name="entrez"/>
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.<ref name="entrez"/>


       <span style="color:blue;">Survival evasion peptide</span>                          <span style="color:red;"> Antimicrobial peptide</span>
       <span style="color:blue;">Survival evasion peptide</span>                          <span style="color:red;"> Antimicrobial peptide</span>
   
   
  <span style="color:blue;">YDPEAASAPGSGNPCHEASAAQKENAGEDPGLARQAPKPRKQR</span><span style="color:red;">SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL</span>  
  <span style="color:blue;">YDPEAASAPGSGNPCHEASAAQKENAGEDPGLARQAPKPRKQR</span><span style="color:red;">SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL</span>  
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.<ref name="pmid">{{cite journal  | vauthors=Baechle D, Flad T, Cansier A |title=Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L. |journal=J. Biol. Chem. |volume=281 |issue= 9 |pages= 5406–15 |year= 2006 |pmid= 16354654 |doi= 10.1074/jbc.M504670200 |display-authors=etal}}</ref>
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.<ref name="pmid">{{cite journal  | vauthors=Baechle D, Flad T, Cansier A |title=Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L. |journal=J. Biol. Chem. |volume=281 |issue= 9 |pages= 5406–15 |year= 2006 |pmid= 16354654 |doi= 10.1074/jbc.M504670200 |display-authors=etal}}</ref>


  DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
  DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
Line 17: Line 17:
== Mechanism ==
== Mechanism ==


The crystal structure of dermcidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding.<ref name="pmid23426625">{{PDB|2YMK}}{{cite journal | author = Song, Chen | author2 = Weichbrodt, Conrad | author3 = Salnikov, Evgeniy S | author4 = Dynowski, Marek | author5 = Forsberg, Björn O | author6 = Bechinger, Burkhard | author7 = Steinem, Claudia | author8 = de Groot, Bert L | author9 = Zachariae, Ulrich | author10 = Zeth, Kornelius | title = Crystal structure and functional mechanism of a human antimicrobial membrane channel | journal = PNAS | volume = 110 | issue = 12 | pages = 4586–91|date=Feb 2013 | pmid = 23426625 | pmc =  3607029| doi = 10.1073/pnas.1214739110 }}</ref> 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.
The crystal structure of dermicidin has been solved in solution to reveal a hexameric helix-bundle, mediated by Zn ion binding.<ref name="pmid23426625">{{PDB|2YMK}}{{cite journal | author = Song, Chen | author2 = Weichbrodt, Conrad | author3 = Salnikov, Evgeniy S | author4 = Dynowski, Marek | author5 = Forsberg, Björn O | author6 = Bechinger, Burkhard | author7 = Steinem, Claudia | author8 = de Groot, Bert L | author9 = Zachariae, Ulrich | author10 = Zeth, Kornelius | title = Crystal structure and functional mechanism of a human antimicrobial membrane channel | journal = PNAS | volume = 110 | issue = 12 | pages = 4586–91|date=Feb 2013 | pmid = 23426625 | pmc =  3607029| doi = 10.1073/pnas.1214739110 }}</ref> 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==
==References==
Line 35: Line 35:
*{{cite journal  | vauthors=Monitto CL, Dong SM, Jen J, Sidransky D |title=Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. |journal=Clin. Cancer Res. |volume=10 |issue= 17 |pages= 5862–9 |year= 2005 |pmid= 15355918 |doi= 10.1158/1078-0432.CCR-04-0435 }}
*{{cite journal  | vauthors=Monitto CL, Dong SM, Jen J, Sidransky D |title=Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. |journal=Clin. Cancer Res. |volume=10 |issue= 17 |pages= 5862–9 |year= 2005 |pmid= 15355918 |doi= 10.1158/1078-0432.CCR-04-0435 }}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 |display-authors=etal}}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 |display-authors=etal}}
*{{cite journal  | vauthors=Lai YP, Peng YF, Zuo Y |title=Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide. |journal=Biochem. Biophys. Res. Commun. |volume=328 |issue= 1 |pages= 243–50 |year= 2005 |pmid= 15670776 |doi= 10.1016/j.bbrc.2004.12.143 |display-authors=etal}}
*{{cite journal  | vauthors=Lai YP, Peng YF, Zuo Y |title=Functional and structural characterization of recombinant dermicidin-1L, a human antimicrobial peptide. |journal=Biochem. Biophys. Res. Commun. |volume=328 |issue= 1 |pages= 243–50 |year= 2005 |pmid= 15670776 |doi= 10.1016/j.bbrc.2004.12.143 |display-authors=etal}}
*{{cite journal  | vauthors=Rieg S, Steffen H, Seeber S |title=Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. |journal=J. Immunol. |volume=174 |issue= 12 |pages= 8003–10 |year= 2005 |pmid= 15944307 |doi=  10.4049/jimmunol.174.12.8003|display-authors=etal}}
*{{cite journal  | vauthors=Rieg S, Steffen H, Seeber S |title=Deficiency of dermicidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. |journal=J. Immunol. |volume=174 |issue= 12 |pages= 8003–10 |year= 2005 |pmid= 15944307 |doi=  10.4049/jimmunol.174.12.8003|display-authors=etal}}
*{{cite journal  | vauthors=Watchorn TM, Dowidar N, Dejong CH |title=The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes. |journal=Int. J. Oncol. |volume=27 |issue= 4 |pages= 1105–11 |year= 2006 |pmid= 16142329 |doi=  10.3892/ijo.27.4.1105|display-authors=etal}}
*{{cite journal  | vauthors=Watchorn TM, Dowidar N, Dejong CH |title=The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes. |journal=Int. J. Oncol. |volume=27 |issue= 4 |pages= 1105–11 |year= 2006 |pmid= 16142329 |doi=  10.3892/ijo.27.4.1105|display-authors=etal}}
*{{cite journal  | vauthors=Lowrie AG, Wigmore SJ, Wright DJ |title=Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues. |journal=Br. J. Cancer |volume=94 |issue= 11 |pages= 1663–71 |year= 2006 |pmid= 16685272 |doi= 10.1038/sj.bjc.6603148  | pmc=2361319 |display-authors=etal}}
*{{cite journal  | vauthors=Lowrie AG, Wigmore SJ, Wright DJ |title=dermicidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues. |journal=Br. J. Cancer |volume=94 |issue= 11 |pages= 1663–71 |year= 2006 |pmid= 16685272 |doi= 10.1038/sj.bjc.6603148  | pmc=2361319 |display-authors=etal}}
*{{cite journal  | vauthors=Ewing RM, Chu P, Elisma F |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  1|pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134  | pmc=1847948 |display-authors=etal}}
*{{cite journal  | vauthors=Ewing RM, Chu P, Elisma F |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  1|pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134  | pmc=1847948 |display-authors=etal}}
*{{cite journal  | vauthors=Frum R, Busby SA, Ramamoorthy M |title=HDM2-binding partners: interaction with translation elongation factor EF1alpha. |journal=J. Proteome Res. |volume=6 |issue= 4 |pages= 1410–7 |year= 2007 |pmid= 17373842 |doi= 10.1021/pr060584p |display-authors=etal}}
*{{cite journal  | vauthors=Frum R, Busby SA, Ramamoorthy M |title=HDM2-binding partners: interaction with translation elongation factor EF1alpha. |journal=J. Proteome Res. |volume=6 |issue= 4 |pages= 1410–7 |year= 2007 |pmid= 17373842 |doi= 10.1021/pr060584p |display-authors=etal |pmc=4626875}}
*{{cite journal  | vauthors=Lee Motoyama JP, Kim-Motoyama H, Kim P |title=Identification of dermcidin in human gestational tissue and characterization of its proteolytic activity. |journal=Biochem. Biophys. Res. Commun. |volume=357 |issue= 4 |pages= 828–33 |year= 2007 |pmid= 17448443 |doi= 10.1016/j.bbrc.2007.03.112 |display-authors=etal}}
*{{cite journal  | vauthors=Lee Motoyama JP, Kim-Motoyama H, Kim P |title=Identification of dermicidin in human gestational tissue and characterization of its proteolytic activity. |journal=Biochem. Biophys. Res. Commun. |volume=357 |issue= 4 |pages= 828–33 |year= 2007 |pmid= 17448443 |doi= 10.1016/j.bbrc.2007.03.112 |display-authors=etal}}
{{refend}}
{{refend}}


==External links==
==External links==
* {{MeshName|Dermcidins}}
* {{MeshName|dermicidins}}


{{Pore-forming toxins}}
{{Pore-forming toxins}}


[[Category:Antimicrobial peptides]]
[[Category:Antimicrobial peptides]]

Latest revision as of 20:27, 28 December 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/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.[1][2] It is an anti-microbial peptide[2] 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.[2]

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.[2] 

      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.[3] 

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.[4] 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. ↑ 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.
  2. ↑ 2.0 2.1 2.2 2.3 "Entrez Gene: DCD dermicidin".
  3. ↑ 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.
  4. ↑ 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. PMC 3607029. PMID 23426625.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Dermcidin&oldid=1528411"