Dermcidin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
with 110 amino acids that in humans is encoded by the ''DCD''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
The full-length protein produces derived peptides as proteolysis-inducing factor (PIF) and other
anti-microbial
An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals a ...
peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
,
secreted by human
eccrine sweat gland
Eccrine sweat glands (; from Greek ''ekkrinein'' 'secrete'; sometimes called merocrine glands) are the major sweat glands of the human body, found in virtually all skin, with the highest density in palm and soles, then on the head, but much less ...
s onto the skin as a part of the innate host defense of the immune system. PIF is involved in muscular proteolysis.
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
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
and antifungal activities. The N-terminal peptide, also known as diffusible survival evasion peptide, promotes
neural cell
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
survival under conditions of severe
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
. A glycosylated form of the N-terminal peptide may be associated with
cachexia
Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...
(muscle wasting) in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
patients.
The C-terminal 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
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
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
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
and their residue length. One such active peptide is SSL25, which shows a 2-fold increase in activity against ''
E. coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' compared to DCD-1L.
DCD-1L SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSVL
DCD-1 SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV
SSL25 SSLLEKGLDGAKKAVGGLGKLGKDA
Mechanism
The
crystal structure
In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...
of dermcidin has been solved in solution to reveal a hexameric helix-bundle, mediated by
Zn ion binding.
This is observed to form a tilted channel in membranes under computational examination by
molecular dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of the ...
simulations, and one suggested mechanism of antimicrobial action inferred from this observation is by
ion gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and t ...
decoupling across
biological membranes
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...
. This is supported by concurrent observations in experimental studies of a voltage dependent depolarization of
lipid bilayers
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cell (biology), cells. The cell membranes of almost all organis ...
.
References
Further reading
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External links
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{{Pore-forming toxins
Antimicrobial peptides