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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]

ELN
Identifiers
Aliases ELN, SVAS, WBS, WS, elastin, ADCL1
External IDs OMIM: 130160 GeneCards: ELN
Gene location (Human)
Chromosome 7 (human)
Chr. Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for ELN
Genomic location for ELN
Band 7q11.23 Start 74,027,789 bp[1]
End 74,069,907 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

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

Contents

FunctionEdit

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 significanceEdit

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]

CompositionEdit

 
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 distributionEdit

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]

BiosynthesisEdit

Tropoelastin precursorsEdit

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).

AggregationEdit

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.

CrosslinkingEdit

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 biologyEdit

 
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 alsoEdit

ReferencesEdit

  1. ^ a b c 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. ^ a b c "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. ^ a b c 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 readingEdit

External linksEdit

This article incorporates text from the United States National Library of Medicine, which is in the public domain.