Abstract
Elastin is a major structural component of elastic fibres that provide properties of stretch and recoil to tissues such as arteries, lung and skin. Remarkably, after initial deposition of elastin there is normally no subsequent turnover of this protein over the course of a lifetime. Consequently, elastic fibres must be extremely durable, able to withstand, for example in the human thoracic aorta, billions of cycles of stretch and recoil without mechanical failure. Major defects in the elastin gene (ELN) are associated with a number of disorders including Supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS) and autosomal dominant cutis laxa (ADCL). Given the low turnover of elastin and the requirement for the long term durability of elastic fibres, we examined the possibility for more subtle polymorphisms in the human elastin gene to impact the assembly and long-term durability of the elastic matrix. Surveys of genetic variation resources identified 118 mutations in human ELN, 17 being non-synonymous. Introduction of two of these variants, G422S and K463R, in elastin-like polypeptides as well as full-length tropoelastin, resulted in changes in both their assembly and mechanical properties. Most notably G422S, which occurs in up to 40% of European populations, was found to enhance some elastomeric properties. These studies reveal that even apparently minor polymorphisms in human ELN can impact the assembly and mechanical properties of the elastic matrix, effects that over the course of a lifetime could result in altered susceptibility to cardiovascular disease.
Highlights
Elastin is a polymeric extracellular protein responsible for imparting properties of extensibility and elastic recoil to various tissues found in vertebrate organisms
A further eight potential exonic single nucleotide polymorphisms (SNPs) were identified from analysis of expressed sequence tags, five of which resulted in non-synonymous polymorphisms
This observation may reflect the important role of prolines in initiating b-turns, a structural feature thought to be crucial for assembly and elastomeric properties of the elastic matrix [12,19,20,21]
Summary
Elastin is a polymeric extracellular protein responsible for imparting properties of extensibility and elastic recoil to various tissues found in vertebrate organisms. Elastin is produced as a soluble monomer called tropoelastin Once secreted, it polymerizes, along with other protein components, into elastic fibres that together form an extracellular elastic matrix whose structural integrity is crucial for the mechanical stability and physical properties of the tissue [2]. The human tropoelastin gene is composed of 34 exons, resulting in a protein with an alternating arrangement of hydrophobic and cross-linking domains The former are rich in glycine, proline, alanine, leucine and valine, often organized in short (3–9 amino acids) tandemly repeated sequences forming flexible and highly dynamic structures, including short beta-sheet/beta-turn conformers. These regions are believed to impart elastomeric properties to elastin by a primarily entropic mechanism. These alaninerich crosslinking domains are predicted to be at least partially alpha-helical in nature [2,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
