Histatin
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Histatins are
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...
-rich (cationic) antimicrobial proteins found in
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can ...
. Histatin's involvement in antimicrobial activities makes histatin part 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 ...
. Histatin was first discovered (isolated) in 1988, with functions that's responsible in keeping
homeostasis In biology, homeostasis ( British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
inside the oral cavity, helping in the formation of pellicles, and assist in bonding of metal ions.


Structure

The structure of histatin is unique depending on whether the protein of interest is histatin 1, 3 or 5. Nonetheless, histatins mainly possess a cationic (positive) charge due to the primary structure consisting mostly of basic amino acids. An amino acid that is crucial to histatin's function is histidine. Studies show that the removal of histidine (especially in histatin 5) resulted in reduction of antifungal activity.


Function

Histatins are antimicrobial and antifungal proteins, and have been found to play a role in wound-closure. A significant source of histatins is found in the
serous fluid In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...
secreted by
Ebner's glands Von Ebner's glands, also called Ebner's glands or gustatory glands, are exocrine glands found in the mouth. More specifically, they are serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae ju ...
, salivary glands at the back of the tongue, and produced by
acinus An acinus (; plural, acini; adjective, acinar or acinous) refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry (''acinus'' is Latin for "berry"). The berry-shaped termination of an exocrine gland, where the ...
cells. Here they offer some early defense against incoming microbes. The three major histatins are 1, 3, and 5, which contains 38, 32, and 24 amino acids, respectively. Histatin 2 is a degradation product of histatin 1, and all other histatins are degradation products of Histatin 3 through the process of post-translational
proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...
of the
HTN3 Histatin 3, also known as HTN3, is a protein which in humans is encoded by the ''HTN3'' gene. Function The primary protein encoded by HTN3 is histatin 3. Histatins are a family of small, histidine-rich, salivary proteins, encoded by at least t ...
gene product. Therefore there are only two genes,
HTN1 Histatin-1 is a protein that in humans is encoded by the ''HTN1'' 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 ' ...
and
HTN3 Histatin 3, also known as HTN3, is a protein which in humans is encoded by the ''HTN3'' gene. Function The primary protein encoded by HTN3 is histatin 3. Histatins are a family of small, histidine-rich, salivary proteins, encoded by at least t ...
. The
N-terminus 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 ami ...
of Histatin 5 allows it to bind with metals, and this can result in the production of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
. Histatins disrupt the fungal plasma membrane, resulting in release of the intracellular content of the fungal cell. They also inhibit the growth of
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
, by binding to the potassium transporter and facilitating in the loss of
azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. T ...
- resistant species. The antifungal properties of histatins have been seen with fungi such as ''
Candida glabrata ''Candida glabrata'' is a species of haploid yeast of the genus ''Candida'', previously known as ''Torulopsis glabrata''. Despite the fact that no sexual life cycle has been documented for this species, ''C. glabrata'' strains of both mating t ...
'', ''
Candida krusei ''Candida krusei'' is a budding yeast (a species of fungus) involved in chocolate production. ''Candida krusei'' is an emerging fungal nosocomial pathogen primarily found in the immunocompromised and those with hematological malignancies. It ha ...
'', ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'', and ''
Cryptococcus neoformans ''Cryptococcus neoformans'' is an encapsulated yeast belonging to the class Tremellomycetes and an obligate aerobe that can live in both plants and animals. Its teleomorph is a filamentous fungus, formerly referred to ''Filobasidiella neoformans ...
''. Histatins also precipitate tannins from solution, thus preventing alimentary adsorption.


References

Membrane proteins Antimicrobial peptides {{biochem-stub