Elastin

ELN
Identifiers
AliasesELN, SVAS, WBS, WS, elastin, ADCL1
External IDsOMIM: 130160 GeneCards: ELN
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7q11.23Start74,027,789 bp[1]
End74,069,907 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

2006

n/a

Ensembl

ENSG00000049540

n/a

UniProt

P15502

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 7: 74.03 – 74.07 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Elastin is a highly elastic protein in connective tissue and allows 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. In humans, elastin is encoded by the ELN gene.[3]

Function

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.[4] Multiple transcript variants encoding different isoforms have been found for this gene.[4] Elastin's soluble precursor is tropoelastin.[5] 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.[6]

Clinical significance

Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa.[4] 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.[7]

Composition

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.[7][8] The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries.[9] 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.[10]

Tissue distribution

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 all vertebrates above the jawless fish.[11]

Biosynthesis

Tropoelastin precursors

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 during their export into the extracellular matrix.

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

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

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.[12]

Molecular biology

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.[7]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000049540 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:".
  3. ↑ Curran, Mark E.; Atkinson, Donald L.; Ewart, Amanda K.; Morris, Colleen A.; Leppert, Mark F.; Keating, Mark T. (9 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. Retrieved 26 February 2015.
  4. 1 2 3 "Entrez Gene: elastin".
  5. ↑ "Elastin (ELN)". Retrieved 31 October 2011.
  6. ↑ Muiznieks LD, Weiss AS, Keeley FW (Apr 2010). "Structural disorder and dynamics of elastin". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 88 (2): 239–50. doi:10.1139/o09-161. PMID 20453927.
  7. 1 2 3 Vrhovski, Bernadette; Weiss, Anthony S. (15 November 1998). "Biochemistry of tropoelastin". European Journal of Biochemistry. 258 (1): 1–18. doi:10.1046/j.1432-1327.1998.2580001.x. Retrieved 26 February 2015.
  8. ↑ Kielty CM, Sherratt MJ, Shuttleworth CA (Jul 2002). "Elastic fibres". Journal of Cell Science. 115 (Pt 14): 2817–28. PMID 12082143.
  9. ↑ Fischer GM, Llaurado JG (Aug 1966). "Collagen and elastin content in canine arteries selected from functionally different vascular beds". Circulation Research. 19 (2): 394–399. doi:10.1161/01.res.19.2.394. PMID 5914851.
  10. ↑ Lammers SR, Kao PH, Qi HJ, Hunter K, Lanning C, Albietz J, Hofmeister S, Mecham R, Stenmark KR, Shandas R (Oct 2008). "Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves". American Journal of Physiology. Heart and Circulatory Physiology. 295 (4): H1451-9. doi:10.1152/ajpheart.00127.2008. PMC 2593497. PMID 18660454.
  11. ↑ Sage EH, Gray WR (1977). "Evolution of elastin structure". Advances in Experimental Medicine and Biology. 79: 291–312. doi:10.1007/978-1-4684-9093-0_27. PMID 868643.
  12. ↑ Umeda H, Takeuchi M, Suyama K (Apr 2001). "Two new elastin cross-links having pyridine skeleton. Implication of ammonia in elastin cross-linking in vivo". The Journal of Biological Chemistry. 276 (16): 12579–12587. doi:10.1074/jbc.M009744200. PMID 11278561.

Further reading

  • Jan SL, Chan SC, Fu YC, Lin SJ (Jun 2009). "Elastin gene study of infants with isolated congenital ductus arteriosus aneurysm". Acta Cardiologica. 64 (3): 363–9. doi:10.2143/ac.64.3.2038023. PMID 19593948.
  • Keeley FW, Bellingham CM, Woodhouse KA (Feb 2002). "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". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 357 (1418): 185–9. doi:10.1098/rstb.2001.1027. PMC 1692930. PMID 11911775.
  • 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 (Sep 2009). "Differential regulation of elastic fiber formation by fibulin-4 and -5". The Journal of Biological Chemistry. 284 (36): 24553–67. doi:10.1074/jbc.M109.019364. PMC 2782046. PMID 19570982.
  • Hubmacher D, Cirulis JT, Miao M, Keeley FW, Reinhardt DP (Jan 2010). "Functional consequences of homocysteinylation of the elastic fiber proteins fibrillin-1 and tropoelastin". The Journal of Biological Chemistry. 285 (2): 1188–98. doi:10.1074/jbc.M109.021246. PMC 2801247. PMID 19889633.
  • Coolen NA, Schouten KC, Middelkoop E, Ulrich MM (Jan 2010). "Comparison between human fetal and adult skin". Archives of Dermatological Research. 302 (1): 47–55. doi:10.1007/s00403-009-0989-8. PMC 2799629. PMID 19701759.
  • 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 (Dec 2009). "Integrative predictive model of coronary artery calcification in atherosclerosis". Circulation. 120 (24): 2448–54. doi:10.1161/CIRCULATIONAHA.109.865501. PMC 2810344. PMID 19948975.
  • Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nishigaki Y, Nozawa Y, Yamada Y (Aug 2009). "Association of genetic variants with chronic kidney disease in individuals with different lipid profiles". International Journal of Molecular Medicine. 24 (2): 233–46. doi:10.3892/ijmm_00000226. PMID 19578796.
  • Akima T, Nakanishi K, Suzuki K, Katayama M, Ohsuzu F, Kawai T (Nov 2009). "Soluble elastin decreases in the progress of atheroma formation in human aorta". Circulation Journal. 73 (11): 2154–62. doi:10.1253/circj.cj-09-0104. PMID 19755752.
  • Chen Q, Zhang T, Roshetsky JF, Ouyang Z, Essers J, Fan C, Wang Q, Hinek A, Plow EF, Dicorleto PE (Oct 2009). "Fibulin-4 regulates expression of the tropoelastin gene and consequent elastic-fibre formation by human fibroblasts". The Biochemical Journal. 423 (1): 79–89. doi:10.1042/BJ20090993. PMC 3024593. PMID 19627254.
  • Tintar D, Samouillan V, Dandurand J, Lacabanne C, Pepe A, Bochicchio B, Tamburro AM (Nov 2009). "Human tropoelastin sequence: dynamics of polypeptide coded by exon 6 in solution". Biopolymers. 91 (11): 943–52. doi:10.1002/bip.21282. PMID 19603496.
  • Dyksterhuis LB, Weiss AS (Jun 2010). "Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking". Biochemical and Biophysical Research Communications. 396 (4): 870–3. doi:10.1016/j.bbrc.2010.05.013. PMID 20457133.
  • 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 (May 2010). "Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes". American Journal of Obstetrics and Gynecology. 202 (5): 431.e1–34. doi:10.1016/j.ajog.2010.03.026. PMC 3604889. PMID 20452482.
  • Fan BJ, Figuieredo Sena DR, Pasquale LR, Grosskreutz CL, Rhee DJ, Chen TC, Delbono EA, Haines JL, Wiggs JL (Sep 2010). "Lack of association of polymorphisms in elastin with pseudoexfoliation syndrome and glaucoma". Journal of Glaucoma. 19 (7): 432–436. doi:10.1097/IJG.0b013e3181c4b0fe. PMID 20051886.
  • Bertram C, Hass R (Oct 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): 657–69. doi:10.1016/j.mad.2009.08.001. PMID 19682489.
  • 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 (Jul 2010). "Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease". Gastroenterology. 139 (1): 130–9.e24. doi:10.1053/j.gastro.2010.03.044. PMC 2908261. PMID 20346360.
  • Rosenbloom J (Dec 1984). "Elastin: relation of protein and gene structure to disease". Laboratory Investigation. 51 (6): 605–23. PMID 6150137.
  • Bax DV, Rodgers UR, Bilek MM, Weiss AS (Oct 2009). "Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3". The Journal of Biological Chemistry. 284 (42): 28616–23. doi:10.1074/jbc.M109.017525. PMC 2781405. PMID 19617625.
  • Rodriguez-Revenga L, Iranzo P, Badenas C, Puig S, Carrió A, Milà M (Sep 2004). "A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa". Archives of Dermatology. 140 (9): 1135–9. doi:10.1001/archderm.140.9.1135. PMID 15381555.
  • Micale L, Turturo MG, Fusco C, Augello B, Jurado LA, Izzi C, Digilio MC, Milani D, Lapi E, Zelante L, Merla G (Mar 2010). "Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis". European Journal of Human Genetics. 18 (3): 317–23. doi:10.1038/ejhg.2009.181. PMC 2987220. PMID 19844261.
  • Tzaphlidou M (2004). "The role of collagen and elastin in aged skin: an image processing approach". Micron. 35 (3): 173–7. doi:10.1016/j.micron.2003.11.003. PMID 15036271.

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