Elastin

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.{{cite web |title=Entrez Gene: elastin |url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2006}} Elastin's soluble precursor is tropoelastin.{{cite web|url=http://wiki.medpedia.com/Elastin_%28ELN%29|title=Elastin (ELN)|access-date=31 October 2011|archive-date=13 March 2017|archive-url=https://web.archive.org/web/20170313081010/http://wiki.medpedia.com/Elastin_(ELN)|url-status=dead}}

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.{{cite journal | vauthors = Muiznieks LD, Weiss AS, Keeley FW | title = Structural disorder and dynamics of elastin | journal = Biochemistry and Cell Biology | volume = 88 | issue = 2 | pages = 239–250 | date = April 2010 | pmid = 20453927 | doi = 10.1139/o09-161 }}

Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa. 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.{{cite journal | vauthors = Vrhovski B, Weiss AS | title = Biochemistry of tropoelastin | journal = European Journal of Biochemistry | volume = 258 | issue = 1 | pages = 1–18 | date = November 1998 | pmid = 9851686 | doi = 10.1046/j.1432-1327.1998.2580001.x | doi-access = free }}

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.{{cite web |title=Elastosis |url=https://dermnetnz.org/topics/elastosis/ |website=DermNet NZ |vauthors=Wright B}}

File:Elastin bovine.png

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.{{cite journal | vauthors = Kielty CM, Sherratt MJ, Shuttleworth CA | title = Elastic fibres | journal = Journal of Cell Science | volume = 115 | issue = Pt 14 | pages = 2817–2828 | date = July 2002 | pmid = 12082143 | doi = 10.1242/jcs.115.14.2817 | doi-access = free }} The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries.{{cite journal | vauthors = Fischer GM, Llaurado JG | title = Collagen and elastin content in canine arteries selected from functionally different vascular beds | journal = Circulation Research | volume = 19 | issue = 2 | pages = 394–399 | date = August 1966 | pmid = 5914851 | doi = 10.1161/01.res.19.2.394 | doi-access = free }} 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.{{cite journal | vauthors = Lammers SR, Kao PH, Qi HJ, Hunter K, Lanning C, Albietz J, Hofmeister S, Mecham R, Stenmark KR, Shandas R | display-authors = 6 | title = Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 295 | issue = 4 | pages = H1451–H1459 | date = October 2008 | pmid = 18660454 | pmc = 2593497 | doi = 10.1152/ajpheart.00127.2008 }}

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.{{cite book|year=1977|volume=79|pages=291–312|doi=10.1007/978-1-4684-9093-0_27|pmid=868643|vauthors=Sage EH, Gray WR|chapter=Evolution of Elastin Structure |series=Advances in Experimental Medicine and Biology |title=Elastin and Elastic Tissue|isbn=978-1-4684-9095-4}}

Elastin is a very long-lived protein, with a half-life of over 78 years in humans.{{cite journal | vauthors = Toyama BH, Hetzer MW | title = Protein homeostasis: live long, won't prosper | journal = Nature Reviews. Molecular Cell Biology | volume = 14 | issue = 1 | pages = 55–61 | date = January 2013 | pmid = 23258296 | pmc = 3570024 | doi = 10.1038/nrm3496 }}

The feasibility of using recombinant human tropoelastin to enable elastin fiber production to improve skin flexibility in wounds and scarring has been studied.{{cite journal | vauthors = Souto EB, Ribeiro AF, Ferreira MI, Teixeira MC, Shimojo AA, Soriano JL, Naveros BC, Durazzo A, Lucarini M, Souto SB, Santini A | display-authors = 6 | title = New Nanotechnologies for the Treatment and Repair of Skin Burns Infections | journal = International Journal of Molecular Sciences | volume = 21 | issue = 2 | page = 393 | date = January 2020 | pmid = 31936277 | pmc = 7013843 | doi = 10.3390/ijms21020393 | doi-access = free }}{{cite journal | vauthors = Xie H, Lucchesi L, Zheng B, Ladich E, Pineda T, Merten R, Gregory C, Rutten M, Gregory K | display-authors = 6 | title = Treatment of Burn and Surgical Wounds With Recombinant Human Tropoelastin Produces New Elastin Fibers in Scars | journal = Journal of Burn Care & Research | volume = 38 | issue = 5 | pages = e859–e867 | date = 1 September 2017 | pmid = 28221299 | doi = 10.1097/BCR.0000000000000507 | s2cid = 39251937 }} 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.

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.{{cite journal | vauthors = Valenzuela CD, Wagner WL, Bennett RD, Ysasi AB, Belle JM, Molter K, Straub BK, Wang D, Chen Z, Ackermann M, Tsuda A, Mentzer SJ | display-authors = 6 | title = Extracellular Assembly of the Elastin Cable Line Element in the Developing Lung | journal = Anatomical Record | volume = 300 | issue = 9 | pages = 1670–1679 | date = September 2017 | pmid = 28380679 | pmc = 6315300 | doi = 10.1002/ar.23603 }}

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).

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.

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.{{cite journal | vauthors = Umeda H, Takeuchi M, Suyama K | title = Two new elastin cross-links having pyridine skeleton. Implication of ammonia in elastin cross-linking in vivo | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 12579–12587 | date = April 2001 | pmid = 11278561 | doi = 10.1074/jbc.M009744200 | doi-access = free }}

File:Domain structure human tropoelastin (EN).png

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.

• Cutis laxa
• Elastic fibers
• Elastin receptor
• Resilin: an invertebrate protein
• Williams syndrome

{{Reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Jan SL, Chan SC, Fu YC, Lin SJ | title = Elastin gene study of infants with isolated congenital ductus arteriosus aneurysm | journal = Acta Cardiologica | volume = 64 | issue = 3 | pages = 363–369 | date = June 2009 | pmid = 19593948 | doi = 10.2143/ac.64.3.2038023 | s2cid = 31411296 }}
• {{cite journal | vauthors = Keeley FW, Bellingham CM, Woodhouse KA | title = Elastin as a self-organizing biomaterial: use of recombinantly expressed human elastin polypeptides as a model for investigations of structure and self-assembly of elastin | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 357 | issue = 1418 | pages = 185–189 | date = February 2002 | pmid = 11911775 | pmc = 1692930 | doi = 10.1098/rstb.2001.1027 }}
• {{cite journal | vauthors = Choudhury R, McGovern A, Ridley C, Cain SA, Baldwin A, Wang MC, Guo C, Mironov A, Drymoussi Z, Trump D, Shuttleworth A, Baldock C, Kielty CM | display-authors = 6 | title = Differential regulation of elastic fiber formation by fibulin-4 and -5 | journal = The Journal of Biological Chemistry | volume = 284 | issue = 36 | pages = 24553–24567 | date = September 2009 | pmid = 19570982 | pmc = 2782046 | doi = 10.1074/jbc.M109.019364 | doi-access = free }}
• {{cite journal | vauthors = Hubmacher D, Cirulis JT, Miao M, Keeley FW, Reinhardt DP | title = Functional consequences of homocysteinylation of the elastic fiber proteins fibrillin-1 and tropoelastin | journal = The Journal of Biological Chemistry | volume = 285 | issue = 2 | pages = 1188–1198 | date = January 2010 | pmid = 19889633 | pmc = 2801247 | doi = 10.1074/jbc.M109.021246 | doi-access = free }}
• {{cite journal | vauthors = Coolen NA, Schouten KC, Middelkoop E, Ulrich MM | title = Comparison between human fetal and adult skin | journal = Archives of Dermatological Research | volume = 302 | issue = 1 | pages = 47–55 | date = January 2010 | pmid = 19701759 | pmc = 2799629 | doi = 10.1007/s00403-009-0989-8 }}
• {{cite journal | vauthors = McGeachie M, Ramoni RL, Mychaleckyj JC, Furie KL, Dreyfuss JM, Liu Y, Herrington D, Guo X, Lima JA, Post W, Rotter JI, Rich S, Sale M, Ramoni MF | display-authors = 6 | title = Integrative predictive model of coronary artery calcification in atherosclerosis | journal = Circulation | volume = 120 | issue = 24 | pages = 2448–2454 | date = December 2009 | pmid = 19948975 | pmc = 2810344 | doi = 10.1161/CIRCULATIONAHA.109.865501 }}
• {{cite journal | vauthors = Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nishigaki Y, Nozawa Y, Yamada Y | display-authors = 6 | title = Association of genetic variants with chronic kidney disease in individuals with different lipid profiles | journal = International Journal of Molecular Medicine | volume = 24 | issue = 2 | pages = 233–246 | date = August 2009 | pmid = 19578796 | doi = 10.3892/ijmm_00000226 | doi-access = free }}
• {{cite journal | vauthors = Akima T, Nakanishi K, Suzuki K, Katayama M, Ohsuzu F, Kawai T | title = Soluble elastin decreases in the progress of atheroma formation in human aorta | journal = Circulation Journal | volume = 73 | issue = 11 | pages = 2154–2162 | date = November 2009 | pmid = 19755752 | doi = 10.1253/circj.cj-09-0104 | doi-access = free }}
• {{cite journal | vauthors = Chen Q, Zhang T, Roshetsky JF, Ouyang Z, Essers J, Fan C, Wang Q, Hinek A, Plow EF, Dicorleto PE | display-authors = 6 | title = Fibulin-4 regulates expression of the tropoelastin gene and consequent elastic-fibre formation by human fibroblasts | journal = The Biochemical Journal | volume = 423 | issue = 1 | pages = 79–89 | date = September 2009 | pmid = 19627254 | pmc = 3024593 | doi = 10.1042/BJ20090993 }}
• {{cite journal | vauthors = Tintar D, Samouillan V, Dandurand J, Lacabanne C, Pepe A, Bochicchio B, Tamburro AM | title = Human tropoelastin sequence: dynamics of polypeptide coded by exon 6 in solution | journal = Biopolymers | volume = 91 | issue = 11 | pages = 943–952 | date = November 2009 | pmid = 19603496 | doi = 10.1002/bip.21282 | url = https://oatao.univ-toulouse.fr/8663/8/Tintar_8663.pdf }}
• {{cite journal | vauthors = Dyksterhuis LB, Weiss AS | title = Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking | journal = Biochemical and Biophysical Research Communications | volume = 396 | issue = 4 | pages = 870–873 | date = June 2010 | pmid = 20457133 | doi = 10.1016/j.bbrc.2010.05.013 }}
• {{cite journal | vauthors = Romero R, Velez Edwards DR, Kusanovic JP, Hassan SS, Mazaki-Tovi S, Vaisbuch E, Kim CJ, Chaiworapongsa T, Pearce BD, Friel LA, Bartlett J, Anant MK, Salisbury BA, Vovis GF, Lee MS, Gomez R, Behnke E, Oyarzun E, Tromp G, Williams SM, Menon R | display-authors = 6 | title = Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes | journal = American Journal of Obstetrics and Gynecology | volume = 202 | issue = 5 | pages = 431.e1–431.34 | date = May 2010 | pmid = 20452482 | pmc = 3604889 | doi = 10.1016/j.ajog.2010.03.026 }}
• {{cite journal | vauthors = Fan BJ, Figuieredo Sena DR, Pasquale LR, Grosskreutz CL, Rhee DJ, Chen TC, Delbono EA, Haines JL, Wiggs JL | display-authors = 6 | title = Lack of association of polymorphisms in elastin with pseudoexfoliation syndrome and glaucoma | journal = Journal of Glaucoma | volume = 19 | issue = 7 | pages = 432–436 | date = September 2010 | pmid = 20051886 | pmc = 6748032 | doi = 10.1097/IJG.0b013e3181c4b0fe }}
• {{cite journal | vauthors = Bertram C, Hass R | title = 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 | journal = Mechanisms of Ageing and Development | volume = 130 | issue = 10 | pages = 657–669 | date = October 2009 | pmid = 19682489 | doi = 10.1016/j.mad.2009.08.001 | s2cid = 46477586 }}
• {{cite journal | vauthors = Roberts KE, Kawut SM, Krowka MJ, Brown RS, Trotter JF, Shah V, Peter I, Tighiouart H, Mitra N, Handorf E, Knowles JA, Zacks S, Fallon MB | display-authors = 6 | title = Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease | journal = Gastroenterology | volume = 139 | issue = 1 | pages = 130–9.e24 | date = July 2010 | pmid = 20346360 | pmc = 2908261 | doi = 10.1053/j.gastro.2010.03.044 }}
• {{cite journal | vauthors = Rosenbloom J | title = Elastin: relation of protein and gene structure to disease | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 51 | issue = 6 | pages = 605–623 | date = December 1984 | pmid = 6150137 }}
• {{cite journal | vauthors = Bax DV, Rodgers UR, Bilek MM, Weiss AS | title = Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3 | journal = The Journal of Biological Chemistry | volume = 284 | issue = 42 | pages = 28616–28623 | date = October 2009 | pmid = 19617625 | pmc = 2781405 | doi = 10.1074/jbc.M109.017525 | doi-access = free }}
• {{cite journal | vauthors = Rodriguez-Revenga L, Iranzo P, Badenas C, Puig S, Carrió A, Milà M | title = A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa | journal = Archives of Dermatology | volume = 140 | issue = 9 | pages = 1135–1139 | date = September 2004 | pmid = 15381555 | doi = 10.1001/archderm.140.9.1135 | doi-access = }}
• {{cite journal | vauthors = Micale L, Turturo MG, Fusco C, Augello B, Jurado LA, Izzi C, Digilio MC, Milani D, Lapi E, Zelante L, Merla G | display-authors = 6 | title = Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis | journal = European Journal of Human Genetics | volume = 18 | issue = 3 | pages = 317–323 | date = March 2010 | pmid = 19844261 | pmc = 2987220 | doi = 10.1038/ejhg.2009.181 }}
• {{cite journal | vauthors = Tzaphlidou M | title = The role of collagen and elastin in aged skin: an image processing approach | journal = Micron | volume = 35 | issue = 3 | pages = 173–177 | year = 2004 | pmid = 15036271 | doi = 10.1016/j.micron.2003.11.003 }}

{{refend}}

• {{MeshName|Elastin}}
• {{BUHistology|21402loa}}
• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=williams GeneReviews/NIH/NCBI/UW entry on Williams or Williams-Beuren Syndrome]
• {{usurped|1=[https://web.archive.org/web/20090621191917/http://macromoleculeinsights.com/elastin.php The Elastin Protein]}}
• [http://jcs.biologists.org/cgi/content/full/115/14/2817/FIG2 Microfibril ]

{{NLM content}}

{{Fibrous proteins}}

{{Authority control}}

Category:Aging-related proteins

Category:Biomaterials

Category:Elastomers

Category:Extracellular matrix proteins

Category:Structural proteins