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From Proteopedia
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'''Dermcidin''' is a '''Human''' [https://en.wikipedia.org/wiki/Antimicrobial_peptides_ antimicrobial peptide] of 110 amino acids presents in sweat. 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. | '''Dermcidin''' is a '''Human''' [https://en.wikipedia.org/wiki/Antimicrobial_peptides_ antimicrobial peptide] of 110 amino acids presents in sweat. 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. | ||
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== Expression == | == Expression == | ||
| - | 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. The derived-peptide is then secreted by granules in sweat. | + | Dermcidin gene is located on the '''chromosome 12''' and constitutively expressed as '''precursor''' only in mucous cells of eccrine sweat glands within the dermis of the skin. 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. In that way, many DCD forms could be proteolytically processed. But the most abundant DCD peptide presents in sweat is DCD-1L. | + | The molecular weight of the DCD full-length sequence is 9,3 kDa including the signal peptide. In that way, many DCD forms could be proteolytically processed. But the most abundant DCD peptide presents in sweat is '''DCD-1L'''. |
DCD-1L contains the C-terminal end from the 63 to the 110 residue plus an additional leucine. This peptide is probably created by combination of proteases in sweat. The cathepsin D, 1,10-phenthroline-sensitive carboxypeptidase and an endoprotease are involved in the post-secretory processing of DCD-1L <ref>[[ J. Biol. Chem.-2006-Baechle-5406-15]], </ref>. | DCD-1L contains the C-terminal end from the 63 to the 110 residue plus an additional leucine. This peptide is probably created by combination of proteases in sweat. The cathepsin D, 1,10-phenthroline-sensitive carboxypeptidase and an endoprotease are involved in the post-secretory processing of DCD-1L <ref>[[ J. Biol. Chem.-2006-Baechle-5406-15]], </ref>. | ||
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| - | This form is involved in the [https://en.wikipedia.org/wiki/Innate_immune_system_ 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 : | The Dermcidin peptide sequence has no homology with other known antimicrobial peptides. Two classes of mammalian antimicrobial peptides exist : | ||
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* Monomer : | * 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. | + | 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. Residues involved are charged amino acids such as E, D and H. The N-terminal is cationic whereas the C-terminal is anionic. |
* Assembly of three monomers : | * Assembly of three monomers : | ||
| - | The trimer is formed by salt bridges between 3 subunits. | + | The '''trimer''' is formed by '''salt bridges''' between 3 subunits. These bonds based on the zipper structure 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 cell membrane. |
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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 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. | ||
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== Antimicrobial activity == | == Antimicrobial activity == | ||
| - | They may be effective because the sweat is acidic and composed of salt concentration such as sodium, chloride, potassium and magnesium.This form is involved in the [https://en.wikipedia.org/wiki/Innate_immune_system_ innate immune system] and protect from a variety of pathogenic microorganisms. | + | They may be effective because the sweat is acidic and composed of salt concentration such as sodium, chloride, potassium and magnesium.This form is involved in the [https://en.wikipedia.org/wiki/Innate_immune_system_ innate immune system] and protect from a variety of pathogenic microorganisms. N-ter interact with negatively charges from phospholipid of bacteria membrane ?? |
== Related disease == | == Related disease == | ||
| - | + | atomic dermatitis ... | |
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
Revision as of 20:43, 12 January 2020
| This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115. |
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Dermcidin is a Human antimicrobial peptide of 110 amino acids presents in sweat. 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
Dermcidin gene is located on the chromosome 12 and constitutively expressed as precursor only in mucous cells of eccrine sweat glands within the dermis of the skin. 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. In that way, many DCD forms could be proteolytically processed. But the most abundant DCD peptide presents in sweat is DCD-1L.
DCD-1L contains the C-terminal end from the 63 to the 110 residue plus an additional leucine. This peptide is probably created by combination of proteases in sweat. The cathepsin D, 1,10-phenthroline-sensitive carboxypeptidase and an endoprotease are involved in the post-secretory processing of DCD-1L [1].
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. Residues involved are charged amino acids such as E, D and H. The N-terminal is cationic whereas the C-terminal is anionic.
- Assembly of three monomers :
The trimer is formed by salt bridges between 3 subunits. These bonds based on the zipper structure 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 cell 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
They may be effective because the sweat is acidic and composed of salt concentration such as sodium, chloride, potassium and magnesium.This form is involved in the innate immune system and protect from a variety of pathogenic microorganisms. N-ter interact with negatively charges from phospholipid of bacteria membrane ??
Related disease
atomic dermatitis ...
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
