Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. Tropoelastin is a low complexity protein on both primary and secondary sequence levels. Acta Biomater. The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. 25, 10231029. doi: 10.1006/jmbi.2000.3901, Baldock, C., Oberhauser, A. F., Ma, L., Lammie, D., Siegler, V., Mithieux, S. M., et al. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. Additionally, elastin is remarkably durable as it is primarily deposited during prenatal development and childhood, and is rarely synthesized during adulthood. (1989). Collapse Section. Matrix Biol. (2014). Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. AW gratefully acknowledges NHMRC funding (Ref: 1195827). Biol. Coacervation involves the agglomeration of protein molecules, which is an . J. Exp. Cryo-electron microscopy is a rapidly developing method and likely to contribute to structural knowledge of tropoelastin. Tropoelastin. (2016). doi: 10.1126/scitranslmed.aai7466, PubMed Abstract | CrossRef Full Text | Google Scholar, Avbelj, F. (2000). The hydrophobic domains vary in length, with the majority of the shorter (95 residues) domains occurring near the N-terminus, while the longer (up to 55 residues) domains are found within tropoelastins central and C-terminal regions (Indik et al., 1989). Fibulin-4 and -5, but not fibulin-2, are associated with tropoelastin deposition in elastin-producing cell culture. Importantly, the presence of fibrils indicates that the nanostructures formed during initial assembly contribute to the supramolecular structures that arise during both early (spherule) and later (fibril) stages of elastogenesis. Further down the molecule, the cell-interactive C-terminus was noted to be highly flexible, indicating that high conformational sampling could be conducive to tropoelastins interactions between cell-surface receptors and elastic fiber-associated proteins. Chem. Implications for tissue specificity and durability of elastic tissue. doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. Furthermore, as integrins are involved in the remodeling of the ECM (Bonnans et al., 2014), this is consistent with a model where the tropoelastin-integrin interaction forms part of the wound repair process. For more information, visit Elastagens website atwww.elastagen.com. 25, 492504. doi: 10.1016/j.matbio.2006.10.002, Dyksterhuis, L. B., and Weiss, A. S. (2010). Trends Biotechnol. The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. In addition, Elastagen has received significant support from Australian Federal Government grants and the NSW State Government Medical Devices Fund (MDF). These ordered structures can include -helices and -structures (Vrhovski et al., 1997), which depend on the amino acid content and arrangement of domains (He et al., 2012; Reichheld et al., 2014, 2017; Muiznieks et al., 2015) and the choice of solvent (Reiersen and Rees, 2000; Muiznieks et al., 2015). (2001). Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. Thermal compaction of disordered and elastin-like polypeptides: a temperature-dependent, sequence-specific coarse-grained simulation model. 280, 3052630537. Identification of an elastin cross-linking domain that joins three peptide chains. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). Modulation by elastin peptide VGVAPG of cell proliferation and elastin expression in human skin fibroblasts. It was first hypothesized that tropoelastin assembles in a head-to-tail manner similar to that of other ECM proteins such as collagen, which assembles into fibrils that subsequently associate laterally to form sheets and thicker fibers (Kadler, 2017). doi: 10.1016/j.cis.2010.10.003, Yeo, G. C., Tarakanova, A., Baldock, C., Wise, S. G., Buehler, M. J., and Weiss, A. S. (2016). Figure 1. Sci. doi: 10.1002/bip.360291403, Luo, P., and Baldwin, R. L. (1997). Unlike other companies that use paid endorsements and questionable data, NULASTIN science is proven by 3rd party clinical evaluation. Computational approaches have gained popularity in recent decades as their methodologies have been refined to provide accurate atomistic scale insights into molecular structure and movement (Tarakanova et al., 2018). The most commonly investigated isoform contains domain 26A and lacks domain 22, and is predominantly found in elastic tissues (Indik et al., 1987; Vrhovski et al., 1997). Crosslinking [ edit] Elastogenesis in human aorta: an electron microscopic study. Injectable biomaterial compositions formed from tropoelastin for tissue repair and restoration. doi: 10.1002/ajmg.1320340115, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., et al. Tropoelastin is a flexible molecule that retains its canonical shape. Elastin-like polypeptides as models of intrinsically disordered proteins. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. doi: 10.1016/j.biochi.2004.03.002, Sandberg, L. B., Gray, W. R., Foster, J. Trends towards maximal association are apparent when each of these parameters is varied. Tropoelastins sequence and domain arrangement. The conserved C-terminus is an area of the molecule of particular biological importance in that it is required for both incorporation into elastin and for cellular interactions. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. (2019a). Tropoelastin is an ECM component primarily located in elastic tissues and has been shown to promote the expansion of hematopoietic stem cells (HSCs) and MSCs when used as a substrate coating or as part of the substrate bulk material ().The ECM is proposed to modulate stem cell phenotype and activity, including proliferation, via its chemistry, topography, and mechanical properties (). 2:e1501145. 275, 2844928454. doi: 10.1111/febs.14114, Lent, R. W., Smith, B., Salcedo, L. L., Faris, B., and Franzblau, C. (1969). Chem. doi: 10.1016/s0021-9258(19)43030-5, Dandurand, J., Samouillan, V., Lacabanne, C., Pepe, A., and Bochicchio, B. Tropoelastins C-terminal domain 36 (yellow) does not fall into either category as it contains a distinct sequence capped with a Gly-Arg-Lys-Arg-Lys (GRKRK) motif and is primarily involved in cell interactions. Biochemistry 45, 95189530. Self-healing and thermoreversible rubber from supramolecular assembly. Figure 2. The elasticity of organs and tissues in vertebrates is due to the presence of elastin, and an insoluble protein whose soluble monomer, tropoelastin, is enzymatically cross-linked through -amino groups of lysine residues. doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). Natl. Proc. Furthermore, tropoelastins hydrophobic and cross-linking domains are arranged in alternating patterns throughout the majority of the molecule, giving rise to both inter- and intra-domain level repetition. For example, models involving single point mutations at negatively charged residues demonstrated both regional and global destabilization of tropoelastins structure, which were validated by SAXS structures (Yeo et al., 2012; Tarakanova et al., 2018). 41, 494497. Cellular expression of tropoelastin mRNA splice variants. Additionally, coarse-graining the full-atomistic model has allowed for the examination of mesoscale tropoelastin assembly and, in particular, deciphered the orientation of tropoelastin molecules that occurs during early stage assembly (inset image) (Tarakanova et al., 2019a). (2005). doi: 10.1093/protein/13.11.739, Roberts, S., Dzuricky, M., and Chilkoti, A. (2017). Tropoelastin has 2 alternating domains: (1) hydrophilic, cross-linked, domains rich in Lys and Ala; and (2) hydrophobic domains (responsible for elasticity) rich in Val, Pro, and Gly, which often occur in repeats of VPGVG or VGGVG. The amino acid sequence of domain 36 is unique; furthermore, its sequence confers a positively charged C-terminus comprising lysines between positively charged arginines, forming a RKRK sequence (Vrhovski et al., 1997). 3:100016. doi: 10.1016/j.mtbio.2019.100016, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. doi: 10.1016/j.jmb.2020.08.023, Luan, C. H., Harris, R., Prasad, K. U., and Urry, D. W. (1990). doi: 10.1074/jbc.M004265200, Kadler, K. E. (2017). Biosci. A model two-component system for studying the architecture of elastin assembly in vitro. 27, 441450. Biotechnol., 25 February 2021, View all
300, 13351359. Interactions of fibrillin-1 with heparin/heparan sulfate, implications for microfibrillar assembly. doi: 10.1111/j.1749-6632.1991.tb17013.x, Mecham, R. P., Levy, B. D., Morris, S. L., Madaras, J. G., and Wrenn, D. S. (1985). Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. Allergan's Medical Aesthetics business - a comprehensive portfolio of facial aesthetics, body contouring and plastic and regenerative medicine products - is expected to grow at an 8-10 percent CAGR from 2017 to 2025. doi: 10.1002/bip.22663, Murata, K., and Wolf, M. (2018). For example, the tetrafunctional cross-link, on which the model is based, is derived from porcine elastin (Brown-Augsburger et al., 1995). 43, 131138. Combinations of these two amino acids result in domains that undergo rapid conformational sampling (Rauscher and Pomes, 2017), which, if perturbed toward a conformation that gravitate toward stability, will assemble into highly ordered amyloid-like fibrils that are not elastomeric (Rauscher et al., 2006; Roberts et al., 2015). doi: 10.1016/j.bbagen.2017.07.020, Myers, B., Dubick, M., Last, J. Variations in the relative abundance of alternatively spliced ELN mRNA transcripts have been observed between tissues, and this diversity is thought to be necessary for the fine tuning of the mechanical characteristics of tissues to suit their unique functional requirements (Reichheld et al., 2019). Tropoelastin is the building block of elastin, a key component of the skin, arteries and lungs that gives tissue its elasticity. doi: 10.1038/nrm3904, Bressan, G. M., Castellani, I., Giro, M. G., Volpin, D., Fornieri, C., and Pasquali Ronchetti, I. This reflects the experimentally observed heterogeneity of cross-links in mature elastin, again giving weight to the hypothesis that the flexibility of tropoelastin is imperative for assembly (Schrader et al., 2018; Tarakanova et al., 2019a). doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. J. Pathol. Biol. The full-atomistic model of tropoelastin was developed based on replica exchange molecular dynamics (REMD) simulations, an accelerated sampling method for molecular dynamics (Tarakanova et al., 2018). Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). (1989). Natl. J. Biochem. (2012). J. Biol. 19:e1800250. The compositions include a coalescence-controlling agent in the form of a polysaccharide or polysaccharide derivative, in an amount effective for providing the substance with the properties of flow, enabling injection. Fed. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. It has recently been suggested that fibrillins are capable of stabilizing tropoelastin, possibly for the purpose of selecting conformations that are favorable for elastin assembly (Lockhart-Cairns et al., 2020). 26, 17001709. Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. A. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated . The cross-linking domains are enriched for either Lys-Pro (KP) or Lys-Ala (KA) motifs and form cross-links that link growing tropoelastin chains during elastogenesis; note that exon 6 encodes a KA domain. Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . Synthesis and properties of crosslinked recombinant pro-resilin. Hogan Lovells represented Elastagen Pty Ltd. on the deal. (1995). Instead, tropoelastin domains 1418 and 36 (RKRK sequence) have been found to bind to both integrins. Elastin synthesis during perinatal lung development in the rat. The presence of tropoelastin spherules fusing to fibrils has been noted in native tissue, demonstrating marked similarities between in vitro and in vivo coacervation (Haust et al., 1965; Albert, 1972; Kozel et al., 2006). doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017).