Elastin 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, res ...
that in humans is encoded by the ''ELN''
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 b ...
. Elastin is a key component of the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
in
gnathostomes
Gnathostomata (; from Greek: (') "jaw" + (') "mouth") are the jawed vertebrates. Gnathostome diversity comprises roughly 60,000 species, which accounts for 99% of all living vertebrates, including humans. In addition to opposing jaws, living ...
(jawed vertebrates).
It is highly
elastic
Elastic is a word often used to describe or identify certain types of elastomer, elastic used in garments or stretchable fabrics.
Elastic may also refer to:
Alternative name
* Rubber band, ring-shaped band of rubber used to hold objects togeth ...
and present in
connective tissue allowing many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored.
Function
The ''ELN'' gene encodes a protein that is one of the two components of
elastic fibers
Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and air ...
. The encoded protein is rich in
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, t ...
amino acids such as
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
and
proline, which form mobile hydrophobic regions bounded by crosslinks between
lysine residues.
Multiple transcript variants encoding different isoforms have been found for this gene.
Elastin's soluble precursor is tropoelastin.
The characterization of disorder is consistent with an entropy-driven mechanism of elastic recoil. It is concluded that conformational disorder is a constitutive feature of elastin structure and function.
Clinical significance
Deletions and mutations in this gene are associated with
supravalvular aortic stenosis (SVAS) and the autosomal dominant
cutis laxa
Cutis laxa or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.
Signs and symptoms
It is characterised by skin that is loose, hanging, wrinkled, and lacking in elast ...
.
Other associated defects in elastin include
Marfan syndrome,
emphysema caused by
α1-antitrypsin deficiency,
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
,
Buschke-Ollendorff syndrome,
Menkes syndrome
Menkes disease (MNK), also known as Menkes syndrome, is an X-linked recessive inheritance, X-linked recessive disorder caused by mutations in genes coding for the copper in health, copper-transport protein ATP7A, leading to copper deficiency. Char ...
,
pseudoxanthoma elasticum
Pseudoxanthoma elasticum (PXE) is a genetic disease that causes mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis. PXE is cau ...
, and
Williams syndrome
Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people ...
.
Elastosis
''Elastosis'' is the buildup of elastin in tissues, and is a form of
degenerative disease
Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time.
In neurodegenerative diseases, cells of the central nervous system stop wo ...
.
There are a multitude of causes, but the most commons cause is
actinic elastosis
Actinic elastosis, also known as solar elastosis, is an accumulation of abnormal elastin (elastic tissue) in the dermis of the skin, or in the conjunctiva of the human eye, eye, which occurs as a result of the cumulative effects of prolonged and e ...
of the skin, also known as ''solar elastosis'', which is caused by prolonged and excessive sun exposure, a process known as
photoaging
Photoaging or photoageing (also known as "dermatoheliosis") is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging.
The deterioration ...
. Uncommon causes of skin elastosis include
elastosis perforans serpiginosa,
perforating calcific elastosis and
linear focal elastosis.
[
]
Composition
In the body, elastin is usually associated with other proteins in connective tissues. Elastic fiber in the body is a mixture of amorphous elastin and fibrous fibrillin
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.
Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, whic ...
. Both components are primarily made of smaller amino acid
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 a ...
s such as glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
, valine
Valine (symbol Val or V) is an α-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), an α- carboxylic acid group (which is in the deprotona ...
, alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
, and proline. The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness.
Tissue distribution
Elastin serves an important function in arteries
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
as a medium for pressure wave propagation to help blood flow
Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously m ...
and is particularly abundant in large elastic blood vessels such as the aorta
The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes o ...
. Elastin is also very important in the lungs, elastic ligaments, elastic cartilage
Elastic cartilage, fibroelastic cartilage or yellow fibrocartilage is a type of cartilage present in the pinnae (auricles) of the ear giving it shape, provides shape for the lateral region of the external auditory meatus, medial part of the aud ...
, the skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
, and the bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
. It is present in jawed vertebrates.
Characteristics
Elastin is a very long-lived protein, with a half-life of over 78 years in humans.
Clinical research
The feasibility of using recombinant human tropoelastin to enable elastin fiber production to improve skin flexibility in wounds and scarring has been studied. After subcutaneous injections of recombinant human tropoelastin into fresh wounds it was found there was no improvement in scarring or the flexibility of the eventual scarring.[
]
Biosynthesis
Tropoelastin precursors
Elastin is made by linking together many small soluble
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubi ...
precursor tropoelastin protein molecules (50-70 kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
), to make the final massive insoluble, durable complex. The unlinked tropoelastin molecules are not normally available in the cell, since they become crosslinked into elastin fibres immediately after their synthesis by the cell, after their export into the extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
.
Each tropoelastin consists of a string of 36 small domains, each weighing about 2 kDa in a random coil conformation. The protein consists of alternating hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, t ...
and hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
domains, which are encoded by separate exons, so that the domain structure of tropoelastin reflects the exon organization of the gene. The hydrophilic domains contain Lys-Ala (KA) and Lys-Pro (KP) motifs that are involved in crosslinking during the formation of mature elastin. In the KA domains, lysine residues occur as pairs or triplets separated by two or three alanine residues (e.g. AAAKAAKAA) whereas in KP domains the lysine residues are separated mainly by proline residues (e.g. KPLKP).
Aggregation
Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process called coacervation Coacervate ( or ) is an aqueous phase rich in macromolecules such as synthetic polymers, proteins or nucleic acids. It forms through liquid-liquid phase separation (LLPS), leading to a dense phase in thermodynamic equilibrium with a dilute phase. Th ...
. This process is reversible and thermodynamically controlled and does not require protein cleavage. The coacervate is made insoluble by irreversible crosslinking.
Crosslinking
To make mature elastin fibres, the tropoelastin molecules are cross-linked via their lysine residues with desmosine
Desmosine is an amino acid found uniquely in elastin, a protein found in connective tissue such as skin, lungs, and elastic arteries.
Desmosine is a component of elastin and cross links with its isomer, isodesmosine, giving elasticity to the t ...
and isodesmosine cross-linking molecules. The enzyme that performs the crosslinking is lysyl oxidase
Lysyl oxidase (LOX), also known as protein-lysine 6-oxidase, is an enzyme that, in humans, is encoded by the ''LOX'' gene. It catalyzes the conversion of lysine molecules into highly reactive aldehydes that form cross-links in extracellular matr ...
, using an ''in vivo'' Chichibabin pyridine synthesis reaction.
Molecular biology
In mammals, 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 g ...
only contains one gene for tropoelastin, called ''ELN''. The human ''ELN'' gene is a 45 kb segment on chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 159 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total D ...
, and has 34 exons interrupted by almost 700 introns, with the first exon being a signal peptide assigning its extracellular localization. The large number of introns suggests that genetic recombination may contribute to the instability of the gene, leading to diseases such as SVAS. The expression of tropoelastin mRNA is highly regulated under at least eight different transcription start sites.
Tissue specific variants of elastin are produced by alternative splicing of the tropoelastin gene. There are at least 11 known human tropoelastin isoforms. these isoforms are under developmental regulation, however there are minimal differences among tissues at the same developmental stage.
See also
*Cutis laxa
Cutis laxa or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.
Signs and symptoms
It is characterised by skin that is loose, hanging, wrinkled, and lacking in elast ...
*Elastic fibers
Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and air ...
*Elastin receptor
Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the ''GLB1'' gene.
The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates. The ...
*Resilin
Resilin is an elastomeric protein found in many insects and other arthropods. It provides soft rubber-elasticity to mechanically active organs and tissue; for example, it enables insects of many species to jump or pivot their wings efficiently ...
: an invertebrate protein
*Williams syndrome
Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people ...
References
Further reading
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External links
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GeneReviews/NIH/NCBI/UW entry on Williams or Williams-Beuren Syndrome
The Elastin Protein
Microfibril
{{Authority control
Aging-related proteins
Biomaterials
Elastomers
Extracellular matrix proteins
Structural proteins