Biomacromolecules 20, 11781189. Advanced BioMatrix - Recombinant Tropoelastin, Lyophilized #5052 Proc. doi: 10.1074/jbc.M507309200, Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. Chem. Eng. A., Starcher, B. C., and Urry, D. W. (1974). Codistribution analysis of elastin and related fibrillar proteins in early vertebrate development. doi: 10.1073/pnas.1701877114, Reichheld, S. E., Muiznieks, L. D., Lu, R., Sharpe, S., and Keeley, F. W. (2019). FASEB J. Cooperativity between the hydrophobic and cross-linking domains of elastin. Colloid Interface Sci. (2017). Powered by Madgex Job Board Software. (2019b). U.S.A. 115, 73387343. Moreover, fibulins are essential for elastic fiber directionality, as fibroblasts with fibulin-4 and -5 knockdowns generate poorly formed elastic fibers (Yamauchi et al., 2010), and fibulin-4 / mice display aberrant, poorly cross-linked, and non-fibrous elastin (McLaughlin et al., 2006). Tropoelastin is the soluble precursor of elastin that is secreted as a 60-70-kDa monomer by elastogenic cells such as fibroblasts, lung alveolar cells, chondrocytes, and vascular SMCs [16]. Biosynthesis and nature of elastin structures. 410, 317323. doi: 10.1038/246461a0, Haust, M. D., More, R. H., Bencosme, S. A., and Balis, J. U. 289, 489492. 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). Binding of EDPs to the ERC induces a number of biological effects including migration, adhesion, proliferation, protease expression, and secretion. This review focuses on recent developments that have shaped our current knowledge of elastin assembly through understanding the relationship between tropoelastins structure and function. Acad. J. Biol. A., Torres, A. R., Alvarez, V. L., and Janata, J. doi: 10.1074/jbc.M113.518381, Lee, P., Yeo, G. C., and Weiss, A. S. (2017). The importance of tropoelastins flexibility during self-assembly has also been examined in the light of natural allysine modifications, which condense to give cross-links within mature elastin (discussed further in the following section) (Ozsvar et al., 2019). Parameter, Testing, and Method. 280, 4093940947. The human ELN gene is located on the long arm of chromosome 7q11.2 and comprises of 34 exons nestled between lengthy introns (Indik et al., 1987, 1989; Bashir et al., 1989). Tropoelastins hydrophobic domains are primarily responsible for facilitating coacervation (Tamburro et al., 1992; Miao et al., 2003; Muiznieks et al., 2003). (2018). Rev. Tropoelastin undergoes minimal energy loss during extension, similar to other polymers such as rubber and resilin (Elvin et al., 2005; Cordier et al., 2008; Baldock et al., 2011). Elastin makes up the majority of elastic fibers and is formed by the hierarchical assembly of its monomer, tropoelastin. Banded fibers in tropoelastin coacervates at physiological temperatures. The ERC binds elastin derived peptides, which are the product of proteolytic activity of soluble and insoluble elastin by various elastases. 58, 270277. 27, 441450. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. Chem. A., Rongish, B. J., Czirok, A., Zach, J., Little, C. D., Davis, E. C., et al. FEBS J. Biophys. It's a stretchy protein that resembles a rubber band it can stretch out (extend) and shrink back (recoil). This acquisition and the development of a next generation of injectables based on this technology will ensure Allergan offers innovative filler products for years to come., Robert Daniels, Elastagen CEO, noted: Partnering with Allergan, a leader in medical aesthetics, is incredibly exciting. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). Nat. Chem. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. Calorim. Matrix Biol. A comprehensive map of human elastin cross-linking during elastogenesis. 43, 131138. Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. EBP plays two roles in the assembly of elastin. A new amino acid from hydrolysates of elastin. (1995). Tropoelastin | Circulation: Cardiovascular Imaging (2020). Form. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. (1989). doi: 10.1073/pnas.1812951116, Yue, K., Li, X., Schrobback, K., Sheikhi, A., Annabi, N., Leijten, J., et al. Domains 2736 make up tropoelastins foot, which are labeled as such due to their spatial arrangement, forming an almost claw-like component of the molecule. 149, 282289. doi: 10.1172/jci115204, Sherratt, M., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P., Shuttleworth, C., et al. Fabricating organized elastin in vascular grafts. 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). doi: 10.1016/j.biocel.2008.03.017, Wise, S. G., Yeo, G. C., Hiob, M. A., Rnjak-Kovacina, J., Kaplan, D. L., Ng, M. K., et al. Allergans success is powered by our global colleagues commitment to being Bold for Life. J. Biol. 33, 54685481. The liquid structure of elastin. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. Biophys. Adv. Scientists find way to heal scars left behind by heart attacks Elastic fibers provide tissues with mechanical resilience, durability, and cell interactivity, which support a diverse range of specialized functionality. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). Acad. In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. (2020). 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). Tropoelastin, the raw material used to create 'MeTro' elastic surgical glue developed with the University of Sydney, has been found to encourage stem cell growth - with the potential to ultimately help the body repair itself. Trends Biotechnol. Chem. Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1. Mol. For Allergan, contact: Lisa Brown 1-862-261-7320, 1985 - 2023 BioSpace.com. Rep. 8, 116. This temperature is also known as the transition temperature. (2019). Tropoelastins hydrophobic domains are predominantly responsible for the random coil content of the monomer, and are the result of the unique pairing of proline and glycine pairs that are interspersed throughout the majority of hydrophobic domains (Rauscher and Pomes, 2017). Molecular dynamics modeling of aggregating tropoelastin-derived peptide chains points to the maintenance of a hydrated, disordered, liquid-like state due to the formation of short-lived inter-chain bonds (Rauscher and Pomes, 2017; Reichheld et al., 2020), mostly likely due to the inducement of random coils by PG repeats (vide supra). Elastagen's revolutionary recombinant human tropoelastin, is identical to that present in human tissue and has many clinical applications, including effective breakthrough treatments for acne scars, stretch marks, aesthetic skin repair and wound repair. These interactions trigger a wide range of processes including wound healing, elastogenesis and maintenance of stemness (Yeo and Weiss, 2019). Cell Biol. Chem. Tropoelastin monomers undergo self-assembly upon reaching the transition temperature through the aggregation of their hydrophobic domains (Wise et al., 2014). Collapse Section. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. Bonnans, C., Chou, J., and Werb, Z. 282, 1248412491. Initially, in vitro coacervation is characterized by the rapid aggregation of tropoelastin. Sci. 98, 416. (2006). The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). Indeed, studies examining the consequences of domain insertions and deletions note changes in the intrinsic functionality of tropoelastin, corroborating the hypothesis that domain insertions and deletions result in altered tissue mechanics (Jensen et al., 2000; Kozel et al., 2003; Yeo et al., 2016; Miao et al., 2017). The study is designed to evaluate the efficacy of two formulations of a cross-linked tropoelastin matrix given the product codes ELAPR002f (collectively referred to as ELAPR or ELAPR002) for the treatment of rolling atrophic acne scars when administered as intradermal implants. Assembly proceeds from a nucleation event and undergoes elongation in a step-wise manner to form a multimer which can occur in a head-to-tail fashion (Wise et al., 2014). In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. More recently, it has been demonstrated that KA domains consist of random coil content prior to self-assembly and become more ordered as molecules aggregate, marrying the observations discussed above into a cohesive model within the context of assembly and the requirements of higher-order structures (Reichheld et al., 2014). Tropoelastin: a novel marker for plaque progression and instability. J. Biol. The Weiss Lab's research focuses on the use of human tropoelastin in tissue assembly and wound repair. Tropoelastin cannot readily be prepared in quantity from natural sources and this has limited research in several important areas including structure/function relationships and fiber assembly. 1, 2 Elastogenesis, the process of elastin formation, mainly occurs during the fetal and early neonatal development of organs such as blood vessels, lungs, and skin. Aaron, B., and Gosline, J. The hydrophobic domains contain aliphatic amino acids with proline variations that provide flexibility and the ability to assemble into higher order structures. Crucially, these simulations revealed that self-assembly starts with a nucleation event and elongation proceeds via both globular and fibrillar structures (Tarakanova et al., 2019a). Tropoelastin: a versatile, bioactive assembly module - PubMed doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. Dissection of human tropoelastin: solution structure, dynamics and self-assembly of the exon 5 peptide. Biochim. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. doi: 10.1006/excr.1995.1321, Hinek, A., and Rabinovitch, M. (1994). 28, 432441. Sequence variants of human tropoelastin affecting assembly, structural characteristics and functional properties of polymeric elastin in health and disease. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). Communication: coacervation of tropoelastin results in fiber formation. 1862, 324334. Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly. Eur. Tropoelastin. It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. Cell Biol. Implications for microfibril and elastic fiber assembly. Transglutaminase-mediated cross-linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. Conformational transitions of the cross-linking domains of elastin during self-assembly. doi: 10.1016/j.biomaterials.2017.04.050, Keywords: elastin, elastic fibers, tropoelastin, computational modeling, assembly, Citation: Ozsvar J, Yang C, Cain SA, Baldock C, Tarakanova A and Weiss AS (2021) Tropoelastin and Elastin Assembly. Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. doi: 10.1038/sj.jid.5700047, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Kucich, U., Abrams, W., Rosenbloom, J. C., et al. 150, 154162. Matrix Biol. Elastin and other dermal components are gradually lost through aging, sun damage, and following injury, highlighting a need to replace these components to repair the skin. Res. Biopolymers 107:e23007. Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. Caterpillar | Caterpillar to Relocate Global Headquarters to Dallas We are making enrolling in text alerts easier than ever. 260, 32553258. 284, 22162230. doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). Chem. Elastin synthesis in arterial smooth muscle cell culture. I thank my team at the University of Sydney and greatly look forward to seeing our science commercialized by Allergan.. 249, 997998. Elastic fibers are an important component of the extracellular matrix, providing stretch, resilience, and cell interactivity to a broad range of elastic tissues. doi: 10.1002/ajmg.1320340115, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., et al. doi: 10.1002/bip.360291403, Luo, P., and Baldwin, R. L. (1997). The first successful experiments to define the 3D envelope of tropoelastin utilized small angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) (Baldock et al., 2011). doi: 10.1016/0378-1119(94)00848-m, McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. Effect of peptide sequence on the LCST-like transition of elastin-like peptides and elastin-like peptidecollagen-like peptide conjugates: simulations and experiments. J. Struct. Res. The ELN gene provides instructions for making a protein called tropoelastin. Characterization of an unusual tropoelastin with truncated C-terminus in the frog. 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). Natl. Elastin synthesis during perinatal lung development in the rat. 624, 137146. Shape of tropoelastin, the highly extensible protein that - PNAS Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). (2020). doi: 10.1161/circimaging.117.007303, Prhashanna, A., Taylor, P. A., Qin, J., Kiick, K. L., and Jayaraman, A. IRVING, Texas (AP) IRVING, Texas (AP) Fluor Corp. (FLR) on Tuesday reported fourth-quarter net income of $9 million, after reporting a loss in the same period a year earlier. (1973). Allergan Snaps Up Sydney Biotech for Upfront Payment of US $95M The lysines of domain 15 and 17 are believed to play key roles in this interaction. Evidence for the presence of alpha-aminoadipic acid delta-semialdehyde and its aldol condensation product. Exon 26-coded polypeptide: an isolated hydrophobic domain of human tropoelastin able to self-assemble in vitro. Chem. Tropoelastin massively associates during coacervation to form quantized protein spheres. Int. Recycling of the 67-kDa elastin binding protein in arterial myocytes is imperative for secretion of tropoelastin. [Epub ahead of print]. Due to the lack of a full-atomistic structure, a number of elastin derivatives, including isolated tropoelastin domains (Toonkool et al., 2001; Mackay et al., 2005; Dyksterhuis et al., 2007; Dyksterhuis and Weiss, 2010) and synthetic elastin-derived peptides (EDPs) (Luan et al., 1990; Tamburro et al., 1992; Kentsis and Sosnick, 1998; Kumashiro et al., 2006; Reichheld et al., 2014, 2017; Muiznieks et al., 2015; MacEwan et al., 2017; Tarakanova et al., 2017) have been studied to understand tropoelastins domain level properties. More surprisingly, tropoelastins cross-linking domains are also capable of similar transitions between ordered and disordered structures. Adv. Specific instructions are found in the Directions for Use. Interactions with these integrins on the surface of mesenchymal stem cells, either through surface bound or as soluble tropoelastin, promote MSC proliferation and phenotypic maintenance via FAK and PKB/AKT (Yeo and Weiss, 2019).
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