Elastin

Elastin

Elastin
Identifiers
Symbols  ; SVAS; WBS; WS
External IDs GeneCards:
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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.[1]

Contents

  • Function 1
  • Clinical significance 2
  • Composition 3
  • Molecular biology 4
  • Tissue distribution 5
  • See also 6
  • References 7
  • Further reading 8
  • External links 9

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.[2] Multiple transcript variants encoding different isoforms have been found for this gene.[2] The other name for elastin is tropoelastin.[3] 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.[4]

Clinical significance

Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and the autosomal dominant cutis laxa.[2] 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.[5]

Composition

Elastic fiber is composed mainly of an amorphous component, which is extensively cross-linked elastin, and a fibrillar component, which are primarily the microfibrils such as fibrillin, both of which are made of simple amino acids such as glycine, valine, alanine, and proline.[5][6] The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canine arteries.[7] 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.[8] Elastin is made by linking many soluble tropoelastin protein molecules, in a reaction catalyzed by lysyl oxidase, to make a massive insoluble, durable complex cross-linked by desmosine and isodesmosine in an in vivo Chichibabin pyridine synthesis reaction.[9] The amino acid responsible for these cross-links is lysine. Tropoelastin is a specialized protein with a molecular weight of 64 to 66 kDa, and an irregular or random coil conformation made up of 830 amino acids.

Molecular biology

In mammals, only a single gene for ELN is present. In humans, the ELN gene is a 45 kb segment that lies 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. Due to alternative splicing, there are at least 11 known human tropoelastin isoforms, and are under developmental regulation. However, there are minimal differences among tissues at the same developmental stage.[5]

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, the skin, and the bladder, elastic cartilage. It is present in all vertebrates above the jawless fish.[10]

See also

References

  1. ^ 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.  
  2. ^ a b c "Entrez Gene: elastin". 
  3. ^ "Elastin (ELN)". Retrieved 31 October 2011. 
  4. ^ 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.  
  5. ^ a b c Vrhovski, Bernadette; Weiss, Anthony S. (15 November 1998). "Biochemistry of tropoelastin". European Journal of Biochemistry 258 (1): 1–18.  
  6. ^ Kielty CM, Sherratt MJ, Shuttleworth CA (Jul 2002). "Elastic fibres". Journal of Cell Science 115 (Pt 14): 2817–28.  
  7. ^ 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.  
  8. ^ 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.  
  9. ^ 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.  
  10. ^ Sage EH, Gray WR (1977). "Evolution of elastin structure". Advances in Experimental Medicine and Biology 79: 291–312.  

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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Rosenbloom J (Dec 1984). "Elastin: relation of protein and gene structure to disease". Laboratory Investigation; A Journal of Technical Methods and Pathology 51 (6): 605–23.  
  • 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.  
  • 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.  
  • 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.  
  • Tzaphlidou M (2004). "The role of collagen and elastin in aged skin: an image processing approach". Micron 35 (3): 173–7.  

External links

  • Elastin at the US National Library of Medicine Medical 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 the United States National Library of Medicine, which is in the public domain.