Elastin
Elastinis aproteinencoded by theELNgenein humans. Elastin is a key component in theextracellular matrixofgnathostomes(jawed vertebrates).[5]It is highlyelasticand present inconnective tissueof 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
[edit]TheELNgene encodes a protein that is one of the two components ofelastic fibers.The encoded protein is rich inhydrophobicamino acids such asglycineandproline,which form mobile hydrophobic regions bounded by crosslinks betweenlysineresidues. 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]
Clinical significance
[edit]Deletions and mutations in this gene are associated withsupravalvular aortic stenosis(SVAS) and the autosomal dominantcutis laxa.[8]Other associated defects in elastin includeMarfan syndrome,emphysemacaused byα1-antitrypsindeficiency,atherosclerosis,Buschke–Ollendorff syndrome,Menkes syndrome,pseudoxanthoma elasticum,andWilliams syndrome.[11]
Elastosis
[edit]Elastosisis the buildup of elastin in tissues, and is a form ofdegenerative disease.There are a multitude of causes, but the most commons cause isactinic elastosisof the skin, also known assolar elastosis,which is caused by prolonged and excessive sun exposure, a process known asphotoaging.Uncommon causes of skin elastosis includeelastosis perforans serpiginosa,perforating calcific elastosisandlinear focal elastosis.[12]
| Condition | Distinctive features | Histopathology |
|---|---|---|
| Actinic elastosis (most common, also called solar elastosis) |
Elastin replacing collagen fibers of thepapillary dermisandreticular 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
[edit]
In the body, elastin is usually associated with other proteins in connective tissues.Elastic fiberin the body is a mixture of amorphous elastin and fibrousfibrillin.Both components are primarily made of smalleramino acidssuch 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]
Tissue distribution
[edit]Elastin serves an important function inarteriesas a medium for pressure wave propagation to helpblood flowand is particularly abundant in large elastic blood vessels such as theaorta.Elastin is also very important in thelungs,elastic ligaments,elastic cartilage,theskin,and thebladder.It is present injawed vertebrates.[17]
Characteristics
[edit]Elastin is a very long-lived protein, with a half-life of over 78 years in humans.[18]
Clinical research
[edit]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
[edit]Tropoelastin precursors
[edit]Elastin is made by linking together many smallsolubleprecursortropoelastinprotein 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 alternatinghydrophobicandhydrophilicdomains, 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).
Aggregation
[edit]Tropoelastin aggregates at physiological temperature due to interactions between hydrophobic domains in a process calledcoacervation.This process isreversibleand thermodynamically controlled and does not requireprotein cleavage.The coacervate is made insoluble byirreversiblecrosslinking.
Crosslinking
[edit]To make mature elastin fibres, the tropoelastin molecules are cross-linked via theirlysineresidues withdesmosineandisodesmosinecross-linking molecules. The enzyme that performs the crosslinking islysyl oxidase,using anin vivoChichibabin pyridine synthesisreaction.[22]
Molecular biology
[edit]
In mammals, thegenomeonly contains one gene for tropoelastin, calledELN.The humanELNgene is a 45 kb segment onchromosome 7,and has 34 exons interrupted by almost 700 introns, with the first exon being asignal peptideassigning its extracellular localization. The large number of introns suggests thatgenetic recombinationmay 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 splicingof 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
[edit]- Cutis laxa
- Elastic fibers
- Elastin receptor
- Resilin:an invertebrate protein
- Williams syndrome
References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000049540–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000029675–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^Mithieux SM, Weiss AS (2005). "Elastin".Advances in Protein Chemistry.70:437–461.doi:10.1016/S0065-3233(05)70013-9.ISBN9780120342709.PMID15837523.
- ^Vindin H, Mithieux SM, Weiss AS (November 2019). "Elastin architecture".Matrix Biology.84:4–16.doi:10.1016/j.matbio.2019.07.005.PMID31301399.S2CID196458819.
- ^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.
- ^ab"Entrez Gene: elastin".
- ^"Elastin (ELN)".Archived fromthe originalon 13 March 2017.Retrieved31 October2011.
- ^Muiznieks LD, Weiss AS, Keeley FW (April 2010). "Structural disorder and dynamics of elastin".Biochemistry and Cell Biology.88(2): 239–250.doi:10.1139/o09-161.PMID20453927.
- ^abcVrhovski B, Weiss AS (November 1998)."Biochemistry of tropoelastin".European Journal of Biochemistry.258(1): 1–18.doi:10.1046/j.1432-1327.1998.2580001.x.PMID9851686.
- ^Wright B."Elastosis".DermNet NZ.
- ^abcHosen MJ, Lamoen A, De Paepe A, Vanakker OM (2012)."Histopathology of pseudoxanthoma elasticum and related disorders: histological hallmarks and diagnostic clues".Scientifica.2012:598262.doi:10.6064/2012/598262.PMC3820553.PMID24278718.
-Creative Commons Attribution 3.0 Unportedlicense - ^Kielty CM, Sherratt MJ, Shuttleworth CA (July 2002)."Elastic fibres".Journal of Cell Science.115(Pt 14): 2817–2828.doi:10.1242/jcs.115.14.2817.PMID12082143.
- ^Fischer GM, Llaurado JG (August 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.PMID5914851.
- ^Lammers SR, Kao PH, Qi HJ, Hunter K, Lanning C, Albietz J, et al. (October 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–H1459.doi:10.1152/ajpheart.00127.2008.PMC2593497.PMID18660454.
- ^Sage EH, Gray WR (1977). "Evolution of Elastin Structure".Elastin and Elastic Tissue.Advances in Experimental Medicine and Biology. Vol. 79. pp. 291–312.doi:10.1007/978-1-4684-9093-0_27.ISBN978-1-4684-9095-4.PMID868643.
- ^Toyama BH, Hetzer MW (January 2013)."Protein homeostasis: live long, won't prosper".Nature Reviews. Molecular Cell Biology.14(1): 55–61.doi:10.1038/nrm3496.PMC3570024.PMID23258296.
- ^abSouto EB, Ribeiro AF, Ferreira MI, Teixeira MC, Shimojo AA, Soriano JL, et al. (January 2020)."New Nanotechnologies for the Treatment and Repair of Skin Burns Infections".International Journal of Molecular Sciences.21(2): 393.doi:10.3390/ijms21020393.PMC7013843.PMID31936277.
- ^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.
- ^Valenzuela CD, Wagner WL, Bennett RD, Ysasi AB, Belle JM, Molter K, et al. (September 2017)."Extracellular Assembly of the Elastin Cable Line Element in the Developing Lung".Anatomical Record.300(9): 1670–1679.doi:10.1002/ar.23603.PMC6315300.PMID28380679.
- ^Umeda H, Takeuchi M, Suyama K (April 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.PMID11278561.
Further reading
[edit]- 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.
- Keeley FW, Bellingham CM, Woodhouse KA (February 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): 185–189.doi:10.1098/rstb.2001.1027.PMC1692930.PMID11911775.
- Choudhury R, McGovern A, Ridley C, Cain SA, Baldwin A, Wang MC, et al. (September 2009)."Differential regulation of elastic fiber formation by fibulin-4 and -5".The Journal of Biological Chemistry.284(36): 24553–24567.doi:10.1074/jbc.M109.019364.PMC2782046.PMID19570982.
- Hubmacher D, Cirulis JT, Miao M, Keeley FW, Reinhardt DP (January 2010)."Functional consequences of homocysteinylation of the elastic fiber proteins fibrillin-1 and tropoelastin".The Journal of Biological Chemistry.285(2): 1188–1198.doi:10.1074/jbc.M109.021246.PMC2801247.PMID19889633.
- Coolen NA, Schouten KC, Middelkoop E, Ulrich MM (January 2010)."Comparison between human fetal and adult skin".Archives of Dermatological Research.302(1): 47–55.doi:10.1007/s00403-009-0989-8.PMC2799629.PMID19701759.
- McGeachie M, Ramoni RL, Mychaleckyj JC, Furie KL, Dreyfuss JM, Liu Y, et al. (December 2009)."Integrative predictive model of coronary artery calcification in atherosclerosis".Circulation.120(24): 2448–2454.doi:10.1161/CIRCULATIONAHA.109.865501.PMC2810344.PMID19948975.
- Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, et al. (August 2009)."Association of genetic variants with chronic kidney disease in individuals with different lipid profiles".International Journal of Molecular Medicine.24(2): 233–246.doi:10.3892/ijmm_00000226.PMID19578796.
- Akima T, Nakanishi K, Suzuki K, Katayama M, Ohsuzu F, Kawai T (November 2009)."Soluble elastin decreases in the progress of atheroma formation in human aorta".Circulation Journal.73(11): 2154–2162.doi:10.1253/circj.cj-09-0104.PMID19755752.
- Chen Q, Zhang T, Roshetsky JF, Ouyang Z, Essers J, Fan C, et al. (September 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.PMC3024593.PMID19627254.
- Tintar D, Samouillan V, Dandurand J, Lacabanne C, Pepe A, Bochicchio B, Tamburro AM (November 2009)."Human tropoelastin sequence: dynamics of polypeptide coded by exon 6 in solution"(PDF).Biopolymers.91(11): 943–952.doi:10.1002/bip.21282.PMID19603496.
- 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.
- Romero R, Velez Edwards DR, Kusanovic JP, Hassan SS, Mazaki-Tovi S, Vaisbuch E, et al. (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.e1–431.34.doi:10.1016/j.ajog.2010.03.026.PMC3604889.PMID20452482.
- Fan BJ, Figuieredo Sena DR, Pasquale LR, Grosskreutz CL, Rhee DJ, Chen TC, et al. (September 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.PMC6748032.PMID20051886.
- 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.
- Roberts KE, Kawut SM, Krowka MJ, Brown RS, Trotter JF, Shah V, et al. (July 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.PMC2908261.PMID20346360.
- 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.
- Bax DV, Rodgers UR, Bilek MM, Weiss AS (October 2009)."Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3".The Journal of Biological Chemistry.284(42): 28616–28623.doi:10.1074/jbc.M109.017525.PMC2781405.PMID19617625.
- 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.
- Micale L, Turturo MG, Fusco C, Augello B, Jurado LA, Izzi C, et al. (March 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): 317–323.doi:10.1038/ejhg.2009.181.PMC2987220.PMID19844261.
- Tzaphlidou M (2004). "The role of collagen and elastin in aged skin: an image processing approach".Micron.35(3): 173–177.doi:10.1016/j.micron.2003.11.003.PMID15036271.
External links
[edit]- Elastinat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- Histology image: 21402loa– Histology Learning System at Boston University
- GeneReviews/NIH/NCBI/UW entry on Williams or Williams-Beuren Syndrome
- The Elastin Protein
- Microfibril
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.
