Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

that in humans is encoded by the ''DEFB4'' (defensin, beta 4)

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide discovered in lesional skin.

Structure

hBD-2 is a protein whose primary structure is made by 64 aminoacids. At concentrations ≤2.4 mM, hBD-2 is monomeric. The structure is

amphiphilic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel

beta sheet The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

with strands 2 and 3 in a

beta hairpin The beta hairpin (sometimes also called beta-ribbon or beta-beta unit) is a simple protein structural motif involving two beta strands that look like a Hairpin (fashion), hairpin. The motif consists of two strands that are adjacent in primary stru ...

conformation. The determination of other structural elements depends on the technique used. When X-ray crystallography is used an

alpha helix An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

can be observed at the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

end of the protein (PDB codes: ,, and ). When using NMR this alpha-helix does not appear (PDB code: ), however this structure was determined using a truncated version of hBD-2 which was missing the initial 4 amino acids, and may be the reason for the discrepancy.

Function

Defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct Antimicrobial, antimicrobial activit ...

s form a family of microbicidal and

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

peptides made by

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

s. Members of the defensin family are highly similar in protein sequence. Beta-defensin 2 is an antibiotic peptide which is locally regulated by

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

. Human beta-defensin 2 is produced by a number of

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cells and exhibits potent antimicrobial activity against

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

and '' Candida'', but not Gram-positive '' S. aureus''. It has been speculated that beta-defensin 2 may contribute to the infrequency of Gram-negative infections on skin and lung tissue. hBD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as '' P. aeruginosa'' or cytokines such as TNF-alpha and IL-1 beta. The HBD-2 gene and protein are locally expressed in

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes refer ...

associated with inflammatory skin lesions. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare. Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between hBD-2 and other proteins. One example of this synergistic effect is with epiP, a protein segregated by some strains of '' S. epidermidis''. hBD2, holding hands with epiP, is capable of killing '' S. aureus'', a Gram-positive bacteria responsible of human diseases.

Structure

Function

References

External links

Further reading