Beta defensins are a family of vertebrate

defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, ...

s. The beta defensins are

antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for a ...

implicated in the resistance of epithelial surfaces to microbial colonization. Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified into alpha, beta and theta categories. Every mammalian species explored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils. However, in other species, beta-defensins are more often produced by epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract. Human, rabbit and guinea-pig beta-defensins, as well as human beta-defensin-2 (hBD2), induce the activation and degranulation of mast cells, resulting in the release of histamine and prostaglandin D2.

Genes

β-defensins are coding for genes which impact the function of the

innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

. These genes are responsible for production of

found in

white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

such as

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

granulocytes Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...

and

NK-cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...

, β-defensins are also found in

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

Single-nucleotide polymorphisms In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

(

SNPs In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

) are found in genes coding for β-defensins. The presences of

are lower in the coding regions compared to non-coding regions. The appearance of SNPs in the coding region will highly likely affecting the resistance against infections through changes in the protein sequences which will give rise to different biological functions.

Initiation

Receptors such as

toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...

s (TLR) and nod-like receptors (NLR) will activate the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

by binding of

ligands In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...

such as

lipopolysaccharides Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer me ...

and

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ...

Toll-like receptors Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize st ...

are expressed in intestinal epithelial cells or

antigen presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

(APCs) such as

dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...

B-lymphocytes B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

and

. When the receptors are activated a

cascade reaction A cascade reaction, also known as a domino reaction or tandem reaction, is a chemical process that comprises at least two consecutive reactions such that each subsequent reaction occurs only in virtue of the chemical functionality formed in the p ...

will take place and substances such as

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

and

will be released.

Function

β-defensins are cationic and can therefore interact with the

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...

of invading microbes, which are negative due to

(LPS) and

lipoteichoic acid Lipoteichoic acid (LTA) is a major constituent of the cell wall of gram-positive bacteria. These organisms have an inner (or cytoplasmic) membrane and, external to it, a thick (up to 80 nanometer) peptidoglycan layer. The structure of LTA varies be ...

(LTA) found in the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. The peptides have higher affinity to the binding site compared to Ca2+ and Mg2+ ions. The peptides will therefore exchange place with those ions, thus affecting the stability of the membrane. The peptides have a greater size compared with the ions which cause changes in the membrane structure. Due to changes in the

electric potential The electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as the amount of work energy needed to move a unit of electric charge from a reference point to the specific point in ...

, peptides will pass across the membrane and thus aggregate into dimers. Pore complex will be created as a result of breaking the

hydrogen bonds In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

between the

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 ...

in the terminal end of the strands connecting defensins monomers. Formation of pore complex will cause membrane

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...

and

cell lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...

. Defensins not only have the ability to strengthen the

but can also enhance the

adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

chemotaxis Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...

T-lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

and

mast cells A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

to the infection site. Defensins will also improve the capacity of macrophage phagocytosis.

Avian β-defensins

β-defensins are classified in three classes and Avian β-defensins constitute for one of the classes. This division is based on Zhang's classification and both the length, the

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

of the

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 ...

and the

gene structure Gene structure is the organisation of specialised sequence elements within a gene. Genes contain most of the information necessary for living cells to survive and reproduce. In most organisms, genes are made of DNA, where the particular DNA sequen ...

are factors affecting the classification. Avian β-defensins are separated in avian

heterophile Heterophile antibodies are antibodies induced by external antigens ( heterophile antigens). Some cross-react with self-antigens. For example, in rheumatic fever, antibodies against group A streptococcal cell walls can also react with (and thus ...

s and non-heterophiles. Avian heterophiles can be divided into two sub-classes, depending on the number of present homologous residues in the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

. Avian heterophiles lack protective oxidative mechanisms, such as

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the ...

and

myeloperoxidase Myeloperoxidase (MPO) is a peroxidase enzyme that in humans is encoded by the ''MPO'' gene on chromosome 17. MPO is most abundantly expressed in neutrophil granulocytes (a subtype of white blood cells), and produces hypohalous acids to carry ou ...

. Making non-oxidative mechanisms, such as

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

s and cationic peptides, even more important.

Evolution

β-defensins genes are found across the vertebrates, including mammals, reptiles, birds and fish. The fact that alpha and theta defensins are absence in older vertebrates, like birds and fishes, indicates that defensins must have evolved from the same ancestral gene coding for β-defensins. Indeed, these defensins of this superfamily are related to the 'big defensins' which are found in invertebrate animals, indicating even earlier origins. In 2001, it was thought that β-defensins were similar to the ancestral defensin from a comparison of sequences of β-defensins, α-defensins and insect defensins. Subsequent structural analyses have suggested that the β-defensins, α-defensins, θ-defensins and big defensins share an evolutionary origin, but are separate to the defensins found in insects, fungi and plants. In addition to other antimicrobial defensins, there are related defensin-like proteins with have evolved other functions. These include toxins found in snakes (e.g. crotamine), bearded lizards and platypus.

History

The first beta-defensin discovered was Tracheal Antimicrobial Peptide, found in the bovine airway in 1991. The first human beta-defensin, HBD1, was discovered in 1995, followed by the HBD2 in 1997.

Human proteins containing this domain

DEFB1; DEFB103A;

DEFB105A Beta-defensin 105 is a protein that is encoded by the ''DEFB105A'' gene in humans. Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structu ...

; DEFB105B; DEFB106; DEFB108B;

DEFB109 Beta-defensin 1 is a protein that in humans is encoded by the ''DEFB1'' gene. Defensin, Defensins form a family of microbicidal and cytotoxic peptides made by Neutrophil granulocyte, neutrophils. Members of the defensin family are highly similar ...

; DEFB110; DEFB111; DEFB114; DEFB130; DEFB136; DEFB4; SPAG11A;