A., Gray, W. R., and Franzblau, C. (1973). doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. Adv. doi: 10.1074/jbc.270.30.17778, Cain, S. A., Baldock, C., Gallagher, J., Morgan, A., Bax, D. V., Weiss, A. S., et al. Tropoelastin is a flexible molecule that retains its canonical shape. Cellular expression of tropoelastin mRNA splice variants. doi: 10.1007/s10973-014-4254-9, Debelle, L., and Tamburro, A. M. (1999). Tropoelastins sequence and domain arrangement. Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global biopharmaceutical company. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). 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. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). doi: 10.1016/j.micron.2009.11.003, Urban, Z., Hucthagowder, V., Schrmann, N., Todorovic, V., Zilberberg, L., Choi, J., et al. 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). Bonnans, C., Chou, J., and Werb, Z. Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). Biochim. The flexibility of the mid-region of the molecule was proposed to drive the overall elasticity of the resultant fibers. 84, 6880. Eur. Aaron, B., and Gosline, J. Res. Proc. Comparative genomics of elastin: sequence analysis of a highly repetitive protein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Novel Recombinant Tropoelastin Implants Restore Skin Extracellular Deficient coacervation of two forms of human tropoelastin associated with supravalvular aortic stenosis. doi: 10.1074/jbc.M004265200, Kadler, K. E. (2017). (2003). Solving tropoelastins global structure (Baldock et al., 2011) allowed for 3D mapping on tropoelastin of the approximate locations of domains 10, 19, and 25, which were the first unequivocally cross-linked domains to be discovered (Brown-Augsburger et al., 1995). Tropoelastin was revealed to be an asymmetric molecule with distinct N- and C-terminal regions that are respectively referred to as the head and foot of the molecule. Elastagens 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. Adv. Hogan Lovells represented Elastagen Pty Ltd. on the deal. doi: 10.1002/bip.360291403, Luo, P., and Baldwin, R. L. (1997). Tropoelastin massively associates during coacervation to form quantized protein spheres. doi: 10.1172/jci115204, Sherratt, M., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P., Shuttleworth, C., et al. Ann. Acad. Phase behavior and self-assembly of perfectly sequence-defined and monodisperse multiblock copolypeptides. Package Size. Of most importance, the inability to acquire large quantities of pure tropoelastin historically presented a significant obstacle to experimentally characterizing its structure. For Elastagen contact: Robert Daniels, CEO +61 2 9209 4054. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Received: 17 December 2020; Accepted: 08 February 2021;Published: 25 February 2021. doi: 10.1016/s0021-9258(19)43030-5, Dandurand, J., Samouillan, V., Lacabanne, C., Pepe, A., and Bochicchio, B. Form. This suggests a high level of conformational sampling during this phase of coacervation, indicating that the flexibility of tropoelastin plays a key role in assembly that may persist, to some extent, into later stages of assembly (Reichheld et al., 2020). 10 Endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts produce tropoelastin during the late J. Therm. 11 Articles, This article is part of the Research Topic, Tropoelastin-Cell Receptor Interactions and Implications for Assembly, https://doi.org/10.3389/fbioe.2021.643110, Creative Commons Attribution License (CC BY). Exp. Allergan Plc, a $15.9b provider of medical aesthetics, biosimilars, and over-the-counter pharmaceutical products will acquire Elastagen Pty Ltd., a provider of advanced tissue repair platform based on tropoelastin (gives tissue its elasticity) for $95m.The acquisition adds proprietary injectable products to Allergan's existing portfolio. Multimers may undergo further transitions, such as branching, to form spherules made of multimer aggregates (Tu et al., 2010). Res. (2020). (2019a). Crosslinking [ edit] Chem. 98, 416. Biol. Computational smart polymer design based on elastin protein mutability. 19:e1800250. Sci. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. Stem cell growth accelerated by tropoelastin protein Biopolymers [Epub ahead of print]. 28, 432441. 21:063001. doi: 10.1088/0965-0393/21/6/063001, Tarakanova, A., Huang, W., Weiss, A. S., Kaplan, D. L., and Buehler, M. J. doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017). Domains 12 to 16 of tropoelastin promote cell attachment and spreading doi: 10.1126/sciadv.1501145, Yeo, G. C., and Weiss, A. S. (2019). 31, 261272. J. Biol. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). doi: 10.1021/bi060289i, Tarakanova, A., and Buehler, M. J. (2018). Matrix Biol. Fibulin-4 and -5, but not fibulin-2, are associated with tropoelastin deposition in elastin-producing cell culture. Tropoelastins flexibility does not allow it to pack into a crystal lattice and its size renders it too complex to assign atomic interactions using nuclear magnetic resonance (NMR) on a global level (Tamburro et al., 2003, 2006; Bochicchio et al., 2004; Pepe et al., 2008). 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. 29, 152159. Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. Biol. All rights reserved. 284, 22162230. Allergan is an industry leader in Open Science,a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. Parameter, Testing, and Method. Meanwhile, modifications to the full-atomistic model have revealed the mechanisms that contribute to aberrant fiber structure (Tarakanova et al., 2018) that have been hypothesized to predispose patients to diseases such as acquired cutis laxa (Hu et al., 2006). It has been postulated that the interaction between tropoelastin and cell surface proteoglycans is part of the assembly process of elastin before it is deposited on microfibrils. doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. J. Biochem. Elastagen is an exciting clinical-stage company with an advanced tissue repair platform based on tropoelastin. Chem. (2017). 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. 258, 118. B., Broekelmann, T. J., et al. Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. J. Biol. Thermal compaction of disordered and elastin-like polypeptides: a temperature-dependent, sequence-specific coarse-grained simulation model. 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). (2005). doi: 10.1038/nature06669, Cox, B. J. Biol. 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). This temperature is also known as the transition temperature. Tropoelastin promotes cell attachment and migration of several cell types including fibroblasts, endothelial cells and mesenchymal stem cells. Characterization of an unusual tropoelastin with truncated C-terminus in the frog. (2015). doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). Acad. Although alanine tracts within other proteins are predisposed to -helix formation (Yang and Honig, 1995; Avbelj, 2000), high helical content within tropoelastins KA domains was primarily demonstrated to persist in solvents that stabilize secondary structure, such as trifluoroethanol, rather than aqueous solution (Luo and Baldwin, 1997; Tamburro et al., 2006). 34, 8190. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. Tropoelastin is typically used as a thin coating on tissue culture surfaces. With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives every day. A., Starcher, B. C., and Urry, D. W. (1974). (2008). Acta Biomater. 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. U.S.A. 110, 28522857. Biochemistry 8, 28332837. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Allergen Acquires Elastagen - pharmasalmanac.com 280, 3052630537. J. Struct. Arch. Matrix Biol. doi: 10.1073/pnas.1701877114, Reichheld, S. E., Muiznieks, L. D., Lu, R., Sharpe, S., and Keeley, F. W. (2019). (2015). (1987). Even after being able to produce recombinant tropoelastin at scales suited to characterization studies, traditional techniques have not yet produced an experimentally verified atomistic structure (Martin et al., 1995; Tarakanova and Buehler, 2013). Front. doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). Calorim. The isoform-function theory is further reinforced by the presence of two different ELN genes within teleosts that are differentially expressed both spatially and temporally during development (Miao et al., 2007). Genet. Fluor: Q4 Earnings Snapshot | AP News 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). Localizing alpha-helices in human tropoelastin: assembly of the elastin puzzle. U.S.A. 84, 56805684. Interestingly, the location and orientation of different domains that contacted each other during self-assembly was noted to be heterogeneous, resulting in head-to-head, tail-to-tail, head-to-tail, and lateral interactions (Tarakanova et al., 2019a). Patient Homepage | Accredo The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. U.S.A. 109, 28782883. doi: 10.1016/j.ajhg.2009.09.013. Biol. The smooth muscle cell. Differential expression of two tropoelastin genes in zebrafish. CICADA TURNS 20: How synthetic skin biotech Elastagen changed lives Possible role in nucleated assembly. Mol. 10, 441454. Coacervation characteristics of recombinant human tropoelastin (2005). Am. Micron 32, 185200. Thus, elastin is responsible, in great part, for the properties of elastic fibers. The self-assembly properties and nanostructure of these extra teleost isoforms are yet to be investigated. Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. This process is reversible and thermodynamically controlled and does not require protein cleavage. 149, 282289. The last 17 amino acid residues of the C-terminus of domain 36 are also implicated in HS interactions; the last four residues are Arg-Lys-Arg-Lys and are positively charged at physiological pH which provides a charged cluster capable of binding negatively charged HS (Broekelmann et al., 2005). Annabi, N., Zhang, Y. N., Assmann, A., Sani, E. S., Cheng, G., Lassaletta, A. D., et al. Specific instructions are found in the Directions for Use. (2012). Thus, the current computational model unifies the global and regional characteristics of tropoelastin, inferring mechanisms that complement observed experimental phenomena. Proc. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. Synthesis and structural studies of a pentapeptide sequence of elastin. doi: 10.1016/j.biomaterials.2017.01.041, Tarakanova, A., Ozsvar, J., Weiss, A. S., and Buehler, M. J.
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