Elastin is a
protein that in humans is encoded by the ELNgene. Elastin is a key component of the
extracellular matrix in
gnathostomes (jawed vertebrates).[5] It is highly
elastic and present in
connective tissue allowing many tissues in the body to resume their shape after stretching or contracting.[6] 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.[7]
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.[8] 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]
Accumulation of fragmented elastotic material within the papillary dermis and transcutaneous elimination of elastotic fibers.[13]
Composition
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.[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]
Elastin is a very long-lived protein, with a half-life of over 78 years in humans.[18]
Clinical research
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
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 export into the
extracellular matrix.[21]
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.
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.[11]
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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.
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10.1097/BCR.0000000000000507.
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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.
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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.
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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.
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10.1016/j.mad.2009.08.001.
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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.
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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.
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10.1001/archderm.140.9.1135.
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Tzaphlidou M (2004). "The role of collagen and elastin in aged skin: an image processing approach". Micron. 35 (3): 173–177.
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