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From Proteopedia
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</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
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| + | 1. Song, C. et al. : Crystal Structure and Functional Mechanism of a Human Antimicrobial Membrane Channel. PNAS. 2013 | ||
| + | 2. Maren Paulmann, Thomas Arnold, Dirk Linke, Suat Özdirekcan, Annika Kopp, Thomas Gutsmann, Hubert Kalbacher, Ines Wanke, Verena J. Schuenemann, Michael Habeck, Jochen Bürck, Anne S. Ulrich and Birgit Schittek :Structure-Activity Analysis of the Dermcidin-derived Peptide DCD-1L, an Anionic Antimicrobial Peptide Present in Human Sweat | ||
| + | 3. Birgit Schittek, Rainer Hipfel, Birgit Sauer, Jürgen Bauer, Hubert Kalbacher, Stefan Stevanovic, Markus Schirle, Kristina Schroeder, Nikolaus Blin, Friedegund Meier, Gernot Rassner & Claus Garbe : Dermcidin: a novel human antibiotic peptide secreted by sweat glands | ||
| + | 4. H. Steffen, S. Rieg, I. Wiedemann, H. Kalbacher, M. Deeg, H.-G. Sahl, A. Peschel, F. Götz, C. Garbe, B. Schittek : Naturally Processed Dermcidin-Derived Peptides Do Not Permeabilize Bacterial Membranes and Kill Microorganisms Irrespective of Their Charge. | ||
| + | 5. Zhang, J., Ding, W., Kuai, X., Ji, Y., Zhu, Z., Mao, Z., Wang, Z. : Dermcidin as a novel binding protein of lncRNA STCAT3 and its effect on prognosis in gastric cancer. 2018 | ||
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Dermcidin is a Human antimicrobial peptide of 110 amino acids presents in sweat involved in the regulation of skin flora. This molecule encoded by the DCD gene plays a role in the host defense system as a trimeric channel and thus, is able to prevent infection after injuries or any skin disorders.
Contents |
Expression and function
Dermcidin gene is located on the chromosome 12 and expressed as precursor only in mucous cells of eccrine sweat glands within the dermis of the skin and the derived-peptide is then secreted by granules in sweat.
The molecular weight of the DCD full-length sequence is 9,3 kDa including the signal peptide.
The active form also named DCD-1L contains the C-terminal end from the 63 to the 110 residue and is probably created by combination of proteases in sweat under specific conditions. The cathepsin D, 1,10-phenthroline-sensitive carboxypeptidase and an endoprotease are involved in the post-secretory processing of DCD-1L [1]. The clivage could happen because the sweat is acidic and composed of salt concentration such as sodium, chloride, potassium and magnesium. The cathepsin D with 1,10-phenthroline-sensitive carboxypeptidase and an endoprotease showed processed DCD-1L
This form is involved in the innate immune system and protect from a variety of pathogenic microorganisms.
The Dermcidin peptide sequence has no homology with other known antimicrobial peptides. Two classes of mammalian antimicrobial peptides exist :
- Cathelicidins
- Defensins which are cationic peptides (α-defensins and β-defensins)
But, some size and structural similarities can be found with the defensin family.
Structural highlights
Dermcidin is a channel composed of 3 antiparallel dimers, and has a dimension of about 8x4 nm.
- Monomer :
A monomer is formed by 2 elongated α-helix tied with 2 zinc ions. These Zn2+ ions are linked by N and C-terminal residues from each α-helix. The residues involved are charged amino acids such as E, D and H.
- Assembly of three monomers :
The trimer is formed by salt bridges between 3 subunits. This bonds are managed again by the negatively and positively charged residues so hydrophilic residues. Polar amino acids can be localized in the bond area too. In total, 96 residues are ionizable and which are all facing toward the interior of the tunnel. However, the amino acids pointing toward the exterior are hydrophobic because they are able to interact with the acyl chain of the membrane. They play a role in the internalization in the membrane. The bonds between monomers allow the formation of 6 lateral openings of a diameter of 1 nm. And the presence of small (such as polar amino acids) and positive residues may have an impact on the selection of ion entry.
- The zinc cofactors :
The zinc ions are fundamental as if there are not here, the DCD is no longer a channel. And the high permeability and conductance of the channel is allowed by Zn2+.
Antimicrobial activity
Related disease
This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
</StructureSection>
References
1. Song, C. et al. : Crystal Structure and Functional Mechanism of a Human Antimicrobial Membrane Channel. PNAS. 2013 2. Maren Paulmann, Thomas Arnold, Dirk Linke, Suat Özdirekcan, Annika Kopp, Thomas Gutsmann, Hubert Kalbacher, Ines Wanke, Verena J. Schuenemann, Michael Habeck, Jochen Bürck, Anne S. Ulrich and Birgit Schittek :Structure-Activity Analysis of the Dermcidin-derived Peptide DCD-1L, an Anionic Antimicrobial Peptide Present in Human Sweat 3. Birgit Schittek, Rainer Hipfel, Birgit Sauer, Jürgen Bauer, Hubert Kalbacher, Stefan Stevanovic, Markus Schirle, Kristina Schroeder, Nikolaus Blin, Friedegund Meier, Gernot Rassner & Claus Garbe : Dermcidin: a novel human antibiotic peptide secreted by sweat glands 4. H. Steffen, S. Rieg, I. Wiedemann, H. Kalbacher, M. Deeg, H.-G. Sahl, A. Peschel, F. Götz, C. Garbe, B. Schittek : Naturally Processed Dermcidin-Derived Peptides Do Not Permeabilize Bacterial Membranes and Kill Microorganisms Irrespective of Their Charge. 5. Zhang, J., Ding, W., Kuai, X., Ji, Y., Zhu, Z., Mao, Z., Wang, Z. : Dermcidin as a novel binding protein of lncRNA STCAT3 and its effect on prognosis in gastric cancer. 2018
