tropoelastin allergan

249, 997998. Subtle balance of tropoelastin molecular shape and flexibility Biochemistry 45, 99899996. Acta 761, 1722. Advanced BioMatrix - Recombinant Tropoelastin, Lyophilized #5052 10, 441454. (1987). Characterization of the complete human elastin gene. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). 28, 379382. Acta 303, 363369. Proc. doi: 10.1073/pnas.84.16.5680, Jensen, S. A., Vrhovski, B., and Weiss, A. S. (2000). 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). Res. Natl. doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). Tropoelastin - PubMed FEBS Lett. This content is for members only. doi: 10.1267/ahc.10026, Yang, A. S., and Honig, B. (2020). 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. doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. Chem. J. Struct. Genet. Pharm. doi: 10.1016/j.matbio.2019.06.010, Reichheld, S. E., Muiznieks, L. D., Stahl, R., Simonetti, K., Sharpe, S., and Keeley, F. W. (2014). 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). Eng. Matrix Biol. A., Wachi, H., Davis, E. C., and Mecham, R. P. (2003). Proc. Matrix Biol. Commun. A single tropoelastin molecule can stretch up to eight times its resting length and has a Youngs modulus (tensile stiffness) of 3 kPa (Baldock et al., 2011) in comparison to elastins extensibility of 150% and stiffness of 1 mPa (Aaron and Gosline, 1981). (1995). Isolation and characterization of crosslinked peptides from elastin. (1983). Tropoelastin | Circulation: Cardiovascular Imaging 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. Tropoelastin promotes cell attachment and migration of several cell types including fibroblasts, endothelial cells and mesenchymal stem cells. doi: 10.1093/protein/13.11.739, Roberts, S., Dzuricky, M., and Chilkoti, A. Hydrophobic domains of human tropoelastin interact in a context-dependent manner. Elastins subunit, tropoelastin, is a soluble 6070 kDa protein which has been intensely studied over the past three decades. N. Y. Acad. Proc. (2014). All authors contributed to writing and editing the review. February 14, 2018 Michael Patrini. Biochemistry 8, 28372845. Chem. Eur. 13, 739743. Coacervation optimally occurs at physiological temperature, however, in vitro coacervation can also occur at lower temperatures depending on experimental conditions and the choice of tropoelastin isoform or derivative (Yeo et al., 2011). J. Biol. doi: 10.1016/s0021-9258(19)83613-x, Miao, M., Bellingham, C. M., Stahl, R. J., Sitarz, E. E., Lane, C. J., and Keeley, F. W. (2003). Elastin biomaterials in dermal repair. Non-polar residues are a major contributor to protein folding, as their unfavorable interactions with water drive them to bury into the protein core, however, as tropoelastin is comprised of numerous hydrophobic domains, it has been demonstrated that many of these domains will be at least partially solvent exposed (Dyksterhuis et al., 2007). Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly. FEBS J. 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. [Epub ahead of print]. 79, 277284. 37, 698702. Further to this, the current model of elastin assembly does not account for how long strings or sheets of tropoelastin are capable of forming spherules on a macroscopic scale (Tu et al., 2010). 1862, 324334. Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. Soluble matrix protein is a potent modulator of mesenchymal stem cell The liquid structure of elastin. The alignment of the tropoelastin aggregates . Elastin is a critical skin protein consisting of crosslinked tropoelastin. Biopolymers 103, 563573. "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . doi: 10.1016/j.bbagen.2017.07.020, Myers, B., Dubick, M., Last, J. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. Chem. Arch. Trends Biotechnol. 252, 351365. J. Biol. HS, which is present on cell surface proteoglycans (syndecans and glypicans), interacts strongly with tropoelastin (Cain et al., 2005). Future investigations will allow the bridging of the gap between mesoscale simulations and microscopically observed coacervation (Clarke et al., 2006). Plus 2:100002. doi: 10.1016/j.mbplus.2019.03.001, Parks, W. C., Roby, J. D., Wu, L. C., and Grosso, L. E. (1992). (2014). doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. Natl. Coacervation of recombinant human tropoelastin is strongly influenced by the concentration of protein and NaCl and to a lesser extent on pH. Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). doi: 10.1021/bi034837t, Tamburro, A. M., Guantieri, V., and Gordini, D. D. (1992). doi: 10.1016/j.matbio.2006.10.002, Dyksterhuis, L. B., and Weiss, A. S. (2010). Biomed. Stiffness within the context of self-assembly has also been examined with both coarse grained and full-atomistic simulations using polypeptides derived from tropoelastins hydrophobic domains. A., Rongish, B. J., Czirok, A., Zach, J., Little, C. D., Davis, E. C., et al. Novel Recombinant Tropoelastin Implants Restore Skin - PubMed J. Med. 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). Our Juvederm collection of fillers has sales of over $1 billion globally and is one of the fastest growing parts of our Aesthetics business, said Bill Meury, Chief Commercial Officer at Allergan. Exp. doi: 10.1016/0304-4165(83)90357-4, Narayanan, A. S., Sandberg, L. B., Ross, R., and Layman, D. L. (1976). Figure 3. Fluorescently labelled mesenchymal stem cells growing on tropoelastin. Bochicchio, B., Yeo, G. C., Lee, P., Emul, D., Pepe, A., Laezza, A., et al. Allergans success is powered by our global colleagues commitment to being Bold for Life. For Allergan, contact: Lisa Brown 1-862-261-7320, 1985 - 2023 BioSpace.com. Dissection of human tropoelastin: solution structure, dynamics and self-assembly of the exon 5 peptide. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. The authors wrote and submitted this manuscript in response to an invitation by the Editor. (2015). 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). J. Biol. Hogan Lovells represented Elastagen Pty Ltd. on the deal. 34, 8190. Genet. Res. Am. 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. 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). Biol. It is likely that, as a general rule, integrin binding to tropoelastin is mediated via GAGs, which is facilitated by the repetition of tropoelastins primary sequence and the surface exposure of positively charged similar domains (Lee et al., 2017; Bochicchio et al., 2021). 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: 10.1111/iep.12224, Kentsis, A., and Sosnick, T. R. (1998). Dissection of human tropoelastin: exon-by-exon chemical synthesis and related conformational studies. Rep. 8, 116. 21:063001. doi: 10.1088/0965-0393/21/6/063001, Tarakanova, A., Huang, W., Weiss, A. S., Kaplan, D. L., and Buehler, M. J. 280, 3052630537. 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]. Copyright 2021 Ozsvar, Yang, Cain, Baldock, Tarakanova and Weiss. Tropoelastin. Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). (2017). Allergan to acquire Australian biotech company Elastagen Elastagen was one of the inaugural recipients of MDF funding in 2013 and will be the first to successfully repay the funding amount. U.S.A. 115, 73387343. Trends Biotechnol. Natl. Acta Biomater. Thus, at lower temperatures, the water surrounding these domains forms ordered, clathrate-like shells that prevent aggregation until the appropriate temperature is reached (Wu and Weiss, 1999; Miao et al., 2003; Dandurand et al., 2015). Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. (2015). Res. (2005). Baul, U., Bley, M., and Dzubiella, J. Matrix 12, 156162. Tropoelastin Improves Post-Infarct Cardiac Function doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. (2011). Biochemistry 52, 77317741. Sci. Biochimie 86, 173178. Bashir, M. M., Indik, Z., Yeh, H., Ornstein-Goldstein, N., Rosenbloom, J. C., Abrams, W., et al. 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. Tropoelastin is a precursor protein of elastin, and is composed of hydrophilic (lysine, valine and proline) and hydrophobic (glycine, valine and proline) domains. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. J. Mol. Sci. Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . Trends towards maximal association are apparent when each of these parameters is varied. Biosci. (2015). Struct. It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. Stem cell growth accelerated by tropoelastin protein (2013). This model revealed that tropoelastin maintains a canonical or average structure based on the distribution of its possible conformations in spite of its flexible nature (Figure 2), as well as the possible roles that local structures play in biological processes, specifically, elastogenesis (Tarakanova et al., 2019b). doi: 10.1002/bip.23007, Miao, M., Stahl, R. J., Petersen, L. F., Reintsch, W. E., Davis, E. C., and Keeley, F. W. (2009). doi: 10.1016/j.biomaterials.2017.01.041, Tarakanova, A., Ozsvar, J., Weiss, A. S., and Buehler, M. J. Fluor: Q4 Earnings Snapshot | AP News Pathol. Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. The narrow specificity to v3 and 53 may also be beneficial compared with other ECM adhesion molecules such as fibronectin (which can adhere to up to 20 types of integrin) which may compete with and modulate binding to tropoelastin, and deliver opposing effects on cell proliferation. Allergan's Acquisition of Elastagen - Global Legal Chronicle doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. Tropoelastin interacts with microfibril components including fibrillin-1, fibulin-4, and -5, and other associated molecules such as latent transforming growth factor binding protein-4 (Visconti et al., 2003; McLaughlin et al., 2006; Urban et al., 2009; Yamauchi et al., 2010; Noda et al., 2013; Lockhart-Cairns et al., 2020). Biophys. Biochemistry 36, 84138421. (1983). Acta Gen. Subj. Synthesis and properties of crosslinked recombinant pro-resilin. In addition, Elastagen has received significant support from Australian Federal Government grants and the NSW State Government Medical Devices Fund (MDF). Macromol. Biosynthesis and nature of elastin structures. 293, 1510715119. Fed. doi: 10.1021/bi00835a021, Gray, W. R., Sandberg, L. B., and Foster, J. Dermatol. Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin. (2006). (1989). Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain. Matrix Biol. Gene 154, 159166. Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. (2008). Differential expression of two tropoelastin genes in zebrafish. 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). Elastogenesis is the term that collectively describes the hierarchical process of elastic fiber formation, and is comprised of distinct phases: tropoelastin synthesis, coacervation, cross-linking, and deposition. (1995). Matrix Biol. Biochem. doi: 10.1016/j.actbio.2013.08.003, Wu, W. J., and Weiss, A. S. (1999). doi: 10.1016/s0021-9258(19)43030-5, Dandurand, J., Samouillan, V., Lacabanne, C., Pepe, A., and Bochicchio, B. U.S.A. 110, 28522857. 260, 32553258. Tropoelastin massively associates during coacervation to form quantized protein spheres. Modeling utilizing tropoelastin derivatives has demonstrated that structural compaction into both coils and globules occurs above the transition temperature of self-assembly, which may assist in explaining the anisotropic nature of mature elastin (Baul et al., 2020). The smooth muscle cell. An electron microscopic study. Targeted modulation of tropoelastin structure and assembly. 26, 17001709. The cross-linking domains are defined by lysines, which are responsible for the formation of durable bi-, tri-, and tetrafunctional cross-links within mature elastin. U.S.A. 84, 56805684. Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. 300, 13351359. 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. Biol. Sequence and structure determinants for the self-aggregation of recombinant polypeptides modeled after human elastin. Allergan to Acquire Elastagen to Access Next Generation Injectable Biotechnol. AW is the Scientific Founder of Elastagen Pty. The resultant bending motion rather than scissors-twist motion that stemmed from this stabilization highlights the mutants diminished flexibility as a key driver of impaired fiber assembly in cutis laxa (Tarakanova et al., 2018). Transl. Crosslinking [ edit] 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. (2005). Elastogenesis in human aorta: an electron microscopic study. 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). 278, 1849118498. Attempts to characterize tropoelastins structure have seen a gradual shift from the belief that tropoelastins domains have fixed structures, to understanding that the majority of its domains are capable of transitioning between random coils and transient ordered structures. Biomaterials 139, 163171. Biomacromolecules 20, 11781189. A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors. The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). 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. Acad. J. Biol. Fibulin-4 and -5, but not fibulin-2, are associated with tropoelastin deposition in elastin-producing cell culture. (2018). With the acquisition, Allergan will begin developing a new line that incorporates tropoelastin in the injectable's formula. Coacervation characteristics of recombinant human tropoelastin. doi: 10.1016/j.matbio.2007.05.005, He, D., Miao, M., Sitarz, E. E., Muiznieks, L. D., Reichheld, S., Stahl, R. 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. No use, distribution or reproduction is permitted which does not comply with these terms. 2:e1501145. Cross-linking domains are capable of modulating self-assembly when incorporated into peptides and biomaterials derived from tropoelastins hydrophobic domains. 16,17 We have previously shown that monomeric TE is utilized as a substrate by dermal fibroblasts in the formation of elastin fibroblasts in vitro, where Calorim. Lysinonorleucine. Biophys. A novel cell adhesion region in tropoelastin mediates attachment to integrin alphaVbeta5. Deficient coacervation of two forms of human tropoelastin associated with supravalvular aortic stenosis. B., Broekelmann, T. J., et al. Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. J. Therm. J. Biol. 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). Acta Histochem. This canonical computational structure was determined to be highly similar to the envelope found via SAXS/SANS, where both consist of an extended molecular body accompanied by a protruding foot (Baldock et al., 2011). (1989). Allysine modifications perturb tropoelastin structure and mobility on a local and global scale. However, there are aspects of this model that warrant further investigation. Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. (2009). The Wellcome Trust Centre for Cell-Matrix Research is supported by funding from Wellcome Trust (203128/Z/16/Z). Ann. doi: 10.1074/jbc.M107920200, Tu, Y., and Weiss, A. S. (2010). (2006). Water structure and elastin-like peptide aggregation. Sci. doi: 10.1016/j.matbio.2006.08.258, Clarke, A. W., Arnspang, E. C., Mithieux, S. M., Korkmaz, E., Braet, F., and Weiss, A. S. (2006). doi: 10.1021/acs.biomac.8b01503, Rauscher, S., Baud, S., Miao, M., Keeley, F. W., and Poms, R. (2006). doi: 10.1016/j.biochi.2004.03.002, Sandberg, L. B., Gray, W. R., Foster, J. The hydrophobic domains contain repetitions and variations of Val-Pro-Gly-Val-Gly motifs (Figure 1), resulting in the aforementioned low complexity of sequence (Foster et al., 1973; Gray et al., 1973). Int. doi: 10.1074/jbc.M501390200, Chung, M. I., Miao, M., Stahl, R. J., Chan, E., Parkinson, J., and Keeley, F. W. (2006). doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). 289, 1005710068. Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking. Isolation and characterization of human elastin cDNAs, and age-associated variation in elastin gene expression in cultured skin fibroblasts. Acad. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). In addition to interacting with tropoelastin, fibulin-4 and -5 are capable of also binding LOX and fibrillin-1 and, thus, have key roles in facilitating elastogenesis (Hinderer et al., 2015). 67-kD elastin-binding protein is a protective companion of extracellular insoluble elastin and intracellular tropoelastin. J. Biol. 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. Cell Res. Tropoelastin #5052. doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). (1973). Cross-linking requires the modification of at least one of the lysine participants by a member of the copper-containing LOX or lysine oxidase-like (LOXL) enzyme families. More surprisingly, tropoelastins cross-linking domains are also capable of similar transitions between ordered and disordered structures. Tropoelastin is a flexible molecule that retains its canonical shape. Elastin synthesis in arterial smooth muscle cell culture. Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues. Additionally, elastin is remarkably durable as it is primarily deposited during prenatal development and childhood, and is rarely synthesized during adulthood. Stages of hierarchical assembly of elastic fibers. J. Mol. AT acknowledges support from University of Connecticuts Institute for Collaboration on Health, Intervention, and Policy Faculty Research Seed Grant. Nature 437, 9991002. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. Possible role in nucleated assembly. doi: 10.1016/j.micron.2009.11.003, Urban, Z., Hucthagowder, V., Schrmann, N., Todorovic, V., Zilberberg, L., Choi, J., et al. Caterpillar | Caterpillar to Relocate Global Headquarters to Dallas

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