Thick elastic fibers consisting of bundles of elastin in the human lung
Elastin is aprotein encoded by theELNgene in humans and several other animals. Elastin is a key component in theextracellular matrix ofgnathostomes (jawed vertebrates).[5] It is highlyelastic and present inconnective 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]
TheELN gene encodes a protein that is one of the two components ofelastic fibers. The encoded protein is rich inhydrophobic amino acids such asglycine andproline, which form mobile hydrophobic regions bounded by crosslinks betweenlysine residues. Multiple transcript variants encoding different isoforms have been found for this gene.[8] Elastin's soluble precursor is tropoelastin.[9]
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]
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 fibrousfibrillin. Both components are primarily made of smalleramino acids such asglycine,valine,alanine, andproline.[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]
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]
Elastin is made by linking together many smallsoluble precursortropoelastin protein molecules (50-70kDa), 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 theextracellular matrix.[21]
Each tropoelastin consists of a string of 36 smalldomains, each weighing about 2 kDa in arandom coil conformation. The protein consists of alternatinghydrophobic andhydrophilic domains, which are encoded by separateexons, 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).
Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process calledcoacervation. This process isreversible and thermodynamically controlled and does not requireprotein cleavage. The coacervate is made insoluble byirreversible crosslinking.
In mammals, thegenome only contains one gene for tropoelastin, calledELN. The humanELN gene is a 45 kb segment onchromosome 7, and has 34 exons interrupted by almost 700 introns, with the first exon being asignal peptide assigning its extracellular localization. The large number of introns suggests thatgenetic recombination may contribute to the instability of the gene, leading to diseases such asSVAS. The expression of tropoelastin mRNA is highly regulated under at least eight differenttranscription start sites.
Tissue specific variants of elastin are produced byalternative 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]
^Curran ME, Atkinson DL, Ewart AK, Morris CA, Leppert MF, Keating MT (April 1993). "The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis".Cell.73 (1):159–168.doi:10.1016/0092-8674(93)90168-P.PMID8096434.S2CID8274849.
^abXie H, Lucchesi L, Zheng B, Ladich E, Pineda T, Merten R, et al. (1 September 2017). "Treatment of Burn and Surgical Wounds With Recombinant Human Tropoelastin Produces New Elastin Fibers in Scars".Journal of Burn Care & Research.38 (5):e859 –e867.doi:10.1097/BCR.0000000000000507.PMID28221299.S2CID39251937.
Jan SL, Chan SC, Fu YC, Lin SJ (June 2009). "Elastin gene study of infants with isolated congenital ductus arteriosus aneurysm".Acta Cardiologica.64 (3):363–369.doi:10.2143/ac.64.3.2038023.PMID19593948.S2CID31411296.
Dyksterhuis LB, Weiss AS (June 2010). "Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking".Biochemical and Biophysical Research Communications.396 (4):870–873.doi:10.1016/j.bbrc.2010.05.013.PMID20457133.
Bertram C, Hass R (October 2009). "Cellular senescence of human mammary epithelial cells (HMEC) is associated with an altered MMP-7/HB-EGF signaling and increased formation of elastin-like structures".Mechanisms of Ageing and Development.130 (10):657–669.doi:10.1016/j.mad.2009.08.001.PMID19682489.S2CID46477586.
Rosenbloom J (December 1984). "Elastin: relation of protein and gene structure to disease".Laboratory Investigation; A Journal of Technical Methods and Pathology.51 (6):605–623.PMID6150137.
Rodriguez-Revenga L, Iranzo P, Badenas C, Puig S, Carrió A, Milà M (September 2004). "A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa".Archives of Dermatology.140 (9):1135–1139.doi:10.1001/archderm.140.9.1135.PMID15381555.
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