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Elastin
Elastin
Elastin
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ELN
Identifiers
AliasesELN, SVAS, WBS, WS, elastin, ADCL1
External IDsOMIM: 130160; MGI: 95317; GeneCards: ELN; OMA:ELN - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2006

13717

Ensembl

ENSG00000049540

ENSMUSG00000029675

UniProt

P15502

P54320

RefSeq (mRNA)

NM_007925

RefSeq (protein)

NP_031951

Location (UCSC)Chr 7: 74.03 – 74.07 MbChr 5: 134.73 – 134.78 Mb
PubMed search[3][4]
Wikidata
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Thick elastic fibers consisting of bundles of elastin in the human lung

Elastin is a protein encoded by the ELN gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates).[5] It is highly elastic and present in connective tissue of the body to resume its shape after stretching or contracting.[6] Elastin helps skin return to its original position whence poked or pinched. Elastin is also in important load-bearing tissue of vertebrates and used in places where storage of mechanical energy is required.[7]

Function

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The ELN gene encodes a protein that is one of the two components of elastic fibers. The encoded protein is rich in hydrophobic amino acids such as glycine 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.[8] Elastin's soluble precursor is tropoelastin.[9]

Mechanism of elastic recoil

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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.[10]

Clinical significance

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Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa.[8] Other associated defects in elastin include Marfan syndrome, emphysema caused by α1-antitrypsin deficiency, atherosclerosis, Buschke–Ollendorff syndrome, Menkes syndrome, pseudoxanthoma elasticum, and Williams syndrome.[11]

Elastosis

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Elastosis is the buildup of elastin in tissues, and is a form of degenerative disease. There are a multitude of causes, but the most commons cause is actinic elastosis of the skin, also known as solar elastosis, which is caused by prolonged and excessive sun exposure, a process known as photoaging. Uncommon causes of skin elastosis include elastosis perforans serpiginosa, perforating calcific elastosis and linear focal elastosis.[12]

Skin elastosis causes
Condition Distinctive features Histopathology
Actinic elastosis
(most common, also called solar elastosis) 		Elastin replacing collagen fibers of the papillary dermis and reticular dermis
Elastosis perforans serpiginosa Degenerated elastic fibers and transepidermal perforating canals (arrow in image points at one of them)[13]
Perforating calcific elastosis Clumping of short elastic fibers in the dermis.[13]
Linear focal elastosis Accumulation of fragmented elastotic material within the papillary dermis and transcutaneous elimination of elastotic fibers.[13]

Composition

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Stretched elastin isolated from bovine aorta

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. Both components are primarily made of smaller amino acids such as glycine, valine, alanine, and proline.[11][14] The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries.[15] 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.[16]

Tissue distribution

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Elastin serves an important function in arteries as a medium for pressure wave propagation to help blood flow and is particularly abundant in large elastic blood vessels such as the aorta. Elastin is also very important in the lungs, elastic ligaments, elastic cartilage, the skin, and the bladder. It is present in jawed vertebrates.[17]

Characteristics

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Elastin is a very long-lived protein, with a half-life of over 78 years in humans.[18]

Clinical research

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The feasibility of using recombinant human tropoelastin to enable elastin fiber production to improve skin flexibility in wounds and scarring has been studied.[19][20] 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.[19][20]

Biosynthesis

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Tropoelastin precursors

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Elastin is made by linking together many small soluble precursor tropoelastin protein molecules (50-70 kDa), 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 and export into the extracellular matrix.[21]

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 and hydrophilic 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

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Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process called coacervation. This process is reversible and thermodynamically controlled and does not require protein cleavage. The coacervate is made insoluble by irreversible crosslinking.

Crosslinking

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To make mature elastin fibres, the tropoelastin molecules are cross-linked via their lysine residues with desmosine and isodesmosine cross-linking molecules. The enzyme that performs the crosslinking is lysyl oxidase, using an in vivo Chichibabin pyridine synthesis reaction.[22]

Molecular biology

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Domain structure of human tropoelastin

In mammals, the genome only contains one gene for tropoelastin, called ELN. The human ELN gene is a 45 kb segment on chromosome 7, 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.[11]

See also

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References

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Further reading

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Elastin

View on Grokipedia
from Grokipedia
Elastin is an (ECM) protein that imparts elasticity, extensibility, and to tissues, enabling them to withstand repeated mechanical stress while returning to their original shape. Primarily synthesized during embryonic development and early postnatal periods, it forms insoluble, cross-linked fibers that constitute up to 90% of elastic structures in dynamic organs. With a remarkably long of approximately 70 years, elastin degradation is limited, underscoring its role in long-term tissue resilience. Structurally, elastin derives from the precursor tropoelastin, a 60–72 polypeptide encoded by the ELN gene on human 7q11, which is rich in hydrophobic amino acids such as , , , and (>75% non-polar content). These monomers are secreted by fibroblasts and cells, then enzymatically cross-linked via lysyl oxidase to form mature elastin fibers, often associated with microfibrils like for structural support. The resulting network exhibits low stiffness ( of 0.13–1.5 MPa) and high extensibility (up to 200% elongation), functioning as an efficient storage mechanism through entropic elasticity driven by disordered polypeptide chains. Elastin is most abundant in load-bearing tissues, comprising 28–32% of the dry mass in the , 2–4% in the 's , and significant portions in lungs, , ligaments, and , where it facilitates functions like accommodation, respiratory expansion, and flexibility. Its biomechanical properties—high resilience and reversible deformability—are essential for preventing tissue fatigue, though dysregulation in synthesis or degradation contributes to pathologies like aortic aneurysms and . Regulation involves matrix metalloproteinases (e.g., MMP-2, MMP-9), tissue inhibitors (TIMPs), and signaling molecules such as TGF-β, highlighting elastin's integration into broader ECM .

Structure and Composition

Molecular Structure

Elastin is an insoluble, cross-linked derived from the soluble precursor protein tropoelastin, which is encoded by the ELN gene located on the long arm of human chromosome 7q11.2. Tropoelastin has a molecular weight of approximately 72 kDa and features an unusual amino acid composition dominated by non-polar residues, including over 75% , , , and , while lacking and . This composition contributes to its flexibility and hydrophobicity, enabling the protein's role in elastic tissues. The primary structure of tropoelastin consists of alternating hydrophobic and cross-linking domains, arising from the 34 exons of the ELN gene. Hydrophobic domains, rich in , , , and , adopt beta-turns and disordered coil conformations that provide the structural basis for elasticity. These regions feature repetitive motifs such as VPGVG (valine-proline--valine-glycine), which promote dynamic, irregular secondary structures without stable alpha-helices or beta-sheets. Cross-linking domains, in contrast, are hydrophilic and enriched with residues arranged in motifs like KP (lysine-proline) or KA (lysine-alanine). These undergo oxidative by lysyl to form allysine aldehydes, which then react to create tetrafunctional cross-links, including desmosine and isodesmosine. Such cross-links stabilize the elastin , rendering it insoluble and durable in the . The elasticity of elastin arises from biophysical models emphasizing entropy-driven , where random conformations in the relaxed state maximize disorder. Upon , the hydrophobic domains align, reducing conformational ; relaxation then restores high-entropy randomness, enabling reversible extension up to 200% with minimal energy dissipation. This entropic mechanism, akin to , is facilitated by the disordered coils in hydrophobic regions and the sparse cross-linking that maintains network integrity without rigidity.

Elastic Fibers

Elastic fibers represent a hierarchical assembly within the , consisting of a central amorphous core primarily composed of crosslinked elastin, which accounts for approximately 90% of the fiber's mass, surrounded by a peripheral network of microfibrils rich in that constitute the remaining 10%. These microfibrils, with diameters ranging from 10 to 12 nm, form a scaffold that guides the deposition and organization of the elastin core during fiber maturation. Mature elastic fibers exhibit diameters typically between 0.2 and 1.5 μm, allowing them to bundle into larger structures such as lamellae, particularly in dynamic tissues like arteries where they contribute to overall structural integrity. Interactions between elastin and fibrillin-1 occur through specific binding motifs, such as GxxPG sequences in fibrillin-1 that facilitate association with tropoelastin, the soluble precursor to elastin; additionally, these components support integrin-mediated cell adhesion, enabling cellular interactions with the fiber network via like αvβ3. Visualization of elastic fibers relies on techniques such as , which reveals the beaded appearance of microfibrils surrounding the dense elastin core, and histological staining with Verhoeff's method, which selectively highlights elastic fibers in black against a red for . The structural organization of elastic fibers demonstrates evolutionary conservation across vertebrates, where they provide essential recoil properties to support physiological functions in extensible tissues.

Biosynthesis

Gene Expression and Tropoelastin

The human ELN gene, which encodes the tropoelastin precursor of elastin, is located on chromosome 7q11.23 and spans approximately 45 kb of genomic DNA. It consists of 34 in-frame exons, with exons 34 and 35 having been lost in higher primates, allowing for extensive alternative splicing that generates over 30 distinct mRNA isoforms without disrupting the open reading frame. These isoforms arise primarily from variable inclusion or exclusion of exons such as 22 (often skipped), and alternate splice sites in exons 8, 20, 24, and 26, resulting in tissue-specific variants that may subtly influence elastic fiber assembly and properties, though their precise functional roles remain under investigation. Transcription of the ELN gene is tightly regulated by the GC-rich promoter region, which lacks a and utilizes multiple transcription start sites. Key regulators include the myocardin-related (MRTF), particularly MRTF-A, which acts as a potent coactivator of serum response factor (SRF) to drive ELN expression in vascular cells and fibroblasts during development and injury response. This MRTF/SRF pathway integrates cytoskeletal signals, such as polymerization, to enhance promoter activity, while growth factors like TGF-β1 and IGF-1 further potentiate transcription, contrasting with inhibitory effects from proinflammatory cytokines such as IL-1β and TNF-α. The resulting ELN mRNA is translated on ribosomes associated with the rough (RER) in elastogenic cells, yielding the ~72 kDa tropoelastin polypeptide. In the RER, tropoelastin undergoes limited post-translational modifications to ensure proper folding and stability. residues are hydroxylated to at approximately 20-24% of prolines, catalyzed by prolyl 4-hydroxylase, which contributes to ; this occurs at specific, non-random sites. Unlike many proteins, tropoelastin lacks significant or other modifications such as bond formation, maintaining its hydrophobic character essential for subsequent . Chaperones like BiP and FKBP65 assist in folding, while interaction with elastin-binding protein (EBP) prevents aggregation and targets the protein for export. Tropoelastin is secreted via the classical exocytic pathway, progressing from the RER through the Golgi apparatus for packaging into secretory vesicles. In the trans-Golgi network, the EBP-tropoelastin complex is concentrated into vesicles that fuse with the plasma membrane, releasing the precursor extracellularly through ; this process, observable in fibroblasts and cells, takes about 30 minutes under normal conditions and can be disrupted by agents like brefeldin A (which fuses ER/Golgi) or monensin (which blocks Golgi exit). ELN gene expression exhibits a distinct developmental profile, with peak tropoelastin production occurring during late and the early postnatal period to support rapid formation in growing tissues like the vasculature and lungs. This surge aligns with organ maturation, after which expression declines sharply by , reaching low basal levels in adulthood due to the long (~70 years) of mature elastin, ensuring limited turnover.

Assembly and Crosslinking

Following , tropoelastin undergoes coacervation, a process into globular aggregates driven by hydrophobic interactions between its non-polar domains, particularly those containing Val-Pro-Gly-Val-Gly motifs. This entropically favorable, endothermic event occurs at physiological (around 7.4) and (37°C), where ordered water shells around hydrophobic residues dissipate, enabling association into nanoparticles approximately 200 nm in diameter that further coalesce into 1–2 μm spherules and eventually fibrillar structures. These tropoelastin coacervates align and deposit onto preformed scaffolds composed primarily of fibrillin-1, which provides a beaded filamentous template essential for organized formation. Tropoelastin binds directly to fibrillin-1 via its C-terminal foot domain interacting with the N-terminal region of fibrillin-1, while fibulin-5 acts as a chaperone by bridging tropoelastin aggregates to these , facilitating alignment and preventing premature aggregation. Crosslinking stabilizes the deposited tropoelastin into an insoluble elastin polymer through oxidative of specific residues, catalyzed by the copper-dependent lysyl (LOX) and its paralogs (LOXL1–4). LOX oxidizes the ε-amino group of to form α-aminoadipic-δ-semialdehyde (allysine), which then undergoes spontaneous aldol condensations and reactions to yield unique tetrafunctional crosslinks: desmosine and isodesmosine. These bridges interconnect four tropoelastin chains, typically within lysine-rich alanine-rich (KA) domains, rendering the structure highly stable. The initial oxidation reaction is: Lysine+O2+H2O→LOXAllysine+NH3+H2O2\text{Lysine} + \text{O}_2 + \text{H}_2\text{O} \xrightarrow{\text{LOX}} \text{Allysine} + \text{NH}_3 + \text{H}_2\text{O}_2
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