Powered by Madgex Job Board Software. 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). 3, 4 Elastin has a very low rate of turnover, so it . Thermal compaction of disordered and elastin-like polypeptides: a temperature-dependent, sequence-specific coarse-grained simulation model. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. I thank the Elastagen team for their hard work and dedication in developing our innovative tropoelastin product pipeline and look forward to working with Allergan to take these products to market., Commenting on the transaction, Elastagens founding scientist Prof Anthony Weiss added:Our technology has come a long way from the lab bench at the University of Sydney towards developing products for patients around the world. J. Biochem. Delineation of unusual features in the 5-flanking region. doi: 10.1016/j.jmb.2020.08.023, Luan, C. H., Harris, R., Prasad, K. U., and Urry, D. W. (1990). Received: 17 December 2020; Accepted: 08 February 2021;Published: 25 February 2021. Biochemistry 42, 1334713362. Adv. 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). (2009). Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). 396, 870873. Four days after a heart attack, purified tropoelastin was injected into the heart. Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. Thus, computational approaches can be considered as important means to complement wet bench experiments. 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). The prevention of early self-aggregation in vitro is thought to be mediated by chaperone proteins (Hinek and Rabinovitch, 1994; Miao et al., 2013). Matrix Biol. 25, 492504. (2006). More recently, the computational model of tropoelastin has been leveraged to characterize higher-order structures and probe self-assembly (Tarakanova et al., 2019a). 289, 1005710068. Hogan Lovells represented Elastagen Pty Ltd. on the deal. doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain. Biopolymers 20, 12471260. 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. A. All rights reserved. (2015). Albert, E. N. (1972). 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). 28, 432441. Structure 14, 16671676. doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. 207, 8796. While the clinical stage tropoelastin platform provides multiple opportunities for aesthetics, scar remodelling and tissue repair, it also has the . 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). Biomed. doi: 10.1074/jbc.M507309200, Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). Struct. doi: 10.1021/acs.biomac.6b01759, Mackay, J. P., Muiznieks, L. D., Toonkool, P., and Weiss, A. S. (2005). Bull. doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). Mater. B., Broekelmann, T. J., et al. Chem. Elastin synthesis during perinatal lung development in the rat. 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). Parameter, Testing, and Method. Matrix 12, 156162. (2019a). Elastic fibers are composed of approximately 90% elastin, whilst the remaining components are primarily comprised of fibrillin glycoproteins (Mecham, 1991). J. Hum. Computational models have also been leveraged to pinpoint the molecular consequences of synthetic and disease mutations of tropoelastin. 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). Coarse-grained model of tropoelastin self-assembly into nascent fibrils. 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. doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). doi: 10.1016/j.micron.2009.11.003, Urban, Z., Hucthagowder, V., Schrmann, N., Todorovic, V., Zilberberg, L., Choi, J., et al. Pathol. (1995). Elastin is the major component of elastic fibers, which are a major component of the tissue that supports the body's joints . (2019). Additionally, elastin is remarkably durable as it is primarily deposited during prenatal development and childhood, and is rarely synthesized during adulthood. Natl. 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. Biochim. 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 is a low complexity protein on both primary and secondary sequence levels. 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. Matrix Biol. Proc. The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. Med. EDPs can modulate an array of signal pathways (Scandolera et al., 2016), but full-length tropoelastin does not trigger pathways through the ERC. 10:034102. doi: 10.1088/1748-6041/10/3/034102, Hinek, A., Keeley, F. W., and Callahan, J. Pharm. (1983). Biomacromolecules 21, 35233538. 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). Molecular docking studies utilizing tropoelastin and the 3D structure of LOX1 (Vallet et al., 2018) may assist in our understanding as to whether the enzyme has a preference for modifying particular tropoelastin residues. This review focuses on recent developments that have shaped our current knowledge of elastin assembly through understanding the relationship between tropoelastins structure and function. Molecular modeling of protein materials: case study of elastin. Acta 761, 1722. Ann. Acad. J. Biomol. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry. Unlike hydrophobic domains, cross-linking domains in isolation are unable to self-assemble; thus, they have been studied in the context of the cross-linking of elastin-derived biomaterials (Annabi et al., 2017; Yue et al., 2017). Biochem. (2006). Co-author Professor Anthony Weiss from the Charles Perkins Centre and Faculty of Science explained: "Tropoelastin can repair the heart because it is a precise replica of the body's natural elastic protein,". doi: 10.1016/0005-2795(73)90368-1, Franzblau, C., Faris, B., and Papaioannou, R. (1969). By probing mutations in computational studies that resolve the atomistic structure of the molecule, the deduction of mechanisms associated with changes to functional roles of specific domains has become feasible, and a connection between local structures and biological performance can be established (Figure 2; Tarakanova et al., 2018). Elastin biomaterials in dermal repair. Natl. Dyn. J. Biol. Allergan's Acquisition of Elastagen. In contrast, higher temperatures allow the breaking of the hydrogen bonds of the ordered water, dissipating the clathrate shells and permitting the association of the hydrophobic domains (Yeo et al., 2011). doi: 10.1083/jcb.126.2.563, Hu, Q., Reymond, J. L., Pinel, N., Zabot, M. T., and Urban, Z. 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. 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. Acad. 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). A comprehensive map of human elastin cross-linking during elastogenesis. Chem. Sci. U.S.A. 110, 28522857. ACS Biomater. Trifluoroethanol may form a solvent matrix for assisted hydrophobic interactions between peptide side chains. U.S.A. 108, 43224327. J. Struct. Chemistry 10, 31663176. Dissection of human tropoelastin: exon-by-exon chemical synthesis and related conformational studies. Chem. (2018). 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]. Biol. Elastogenesis occurs during replacement fibrosis in human heart disease and can be accelerated in vitro via tropoelastin treatment. Matrix Biol. The coacervate is made insoluble by irreversible crosslinking. 278, 1849118498. Sci. J. Biol. 2:e1501145. 84, 6880. 289, 14671477. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. (2011). 300, 13351359. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. Acad. For example, the tetrafunctional cross-link, on which the model is based, is derived from porcine elastin (Brown-Augsburger et al., 1995). Latent TGF- binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Forty tropoelastin molecules were subjected to simulations using a MARTINI-based coarse-grained model, integrated with an elastic network model (Tarakanova et al., 2019a). 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). 249, 997998. Tropoelastin. 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 Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. doi: 10.1016/0378-1119(94)00848-m, McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. 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). Cross-linking domains can be subdivided into KP or KA domains, which denote the amino acids (proline or alanine, respectively) that are adjacent to the lysines (Figure 1). (2020). J. Biol. Colloid Interface Sci. Cryo-electron microscopy is a rapidly developing method and likely to contribute to structural knowledge of tropoelastin. The ELN gene provides instructions for making a protein called tropoelastin. Approximately 90% of tropoelastins lysines undergo modification and/or participate in cross-links, indicating that mature elastin is extensively cross-linked (Kozel et al., 2003; Schmelzer et al., 2019). Front. Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. Arch. 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). Its estimated half-life of 70 years (Shapiro et al., 1991) is due to its extensive cross-linking and high hydrophobicity, which render it resistant to degradation (Vrhovski and Weiss, 1998; Schrader et al., 2018; Hedtke et al., 2019). Localizing alpha-helices in human tropoelastin: assembly of the elastin puzzle. Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. doi: 10.1007/978-3-319-71530-8_13-1, Wen, Q., Mithieux, S. M., and Weiss, A. S. (2020). Biomacromolecules 18, 599609. Perturbation of either of these components greatly reduces tropoelastins ability to self-assemble in vitro and interact with the microfibril scaffold of elastic fibers (Nonaka et al., 2014), indicating that an intact domain 36 is required for correct assembly. Elastin is extensively cross-linked and difficult to break apart into monomers even under harsh conditions, thus, initial strategies included feeding animals a copper deficient diet to prevent lysyl oxidase (LOX) cross-linking of tropoelastin; however, this proved inefficient and time consuming (Wise and Weiss, 2009; Tarakanova et al., 2018). 9:643110. doi: 10.3389/fbioe.2021.643110. Allergans success is powered by our global colleagues commitment to being Bold for Life. Commun. 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. Res. A novel cell adhesion region in tropoelastin mediates attachment to integrin alphaVbeta5. 126, 283290. AW is the Scientific Founder of Elastagen Pty. Eng. J. 25, 10231029. (2020). This suggests the ERCs primary signal pathways are involved in wound recognition through fragments of elastin, where EDPs are formed as a result of elastic tissue damage. 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. Proc. doi: 10.1111/iep.12224, Kentsis, A., and Sosnick, T. R. (1998). Of most importance, the inability to acquire large quantities of pure tropoelastin historically presented a significant obstacle to experimentally characterizing its structure. Proc. Biochemistry 45, 99899996. Elastases can be in the form of serine- (e.g., Ela-2), cysteine- (e.g., cathepsin I), or matrix metalloproteinases (MMP-2, -7, -9, and -12), and bioactive peptides include the VGVAPG peptide. doi: 10.1002/mabi.201800250, Tiedemann, K., Batge, B., Muller, P. K., and Reinhardt, D. P. (2001). doi: 10.1046/j.1432-1327.1998.2580001.x, Wang, Z., Liu, L., Mithieux, S. M., and Weiss, A. S. (2020). By leveraging the advantages of computational models, such as elastic network models, full-atomistic models and coarse grained models, as depicted in Figure 2, the correlation between the structure, motions, and the functionality of tropoelastin have recently been explored in depth (Yeo et al., 2016; Tarakanova et al., 2018, 2019a). Cooperativity between the hydrophobic and cross-linking domains of elastin. Elastin is a critical skin protein consisting of crosslinked tropoelastin. 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). Biomacromolecules 20, 11781189. Figure 1. Tropoelastins domains each arise from single exons of the ELN gene. Fell muir lecture: collagen fibril formation in vitro and in vivo. Matrix Biol. Tropoelastin is encoded by the ELN gene, which is present in all vertebrates except jawless fish (Chung et al., 2006). J. Biochem. 43, 131138. Exp. Acta Biomater. doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). CB gratefully acknowledges BBSRC funding (Ref: BB/R008221/1). Pathol. The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). Biol. Domain 26 of tropoelastin plays a dominant role in association by coacervation. Nature 437, 9991002. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. doi: 10.1267/ahc.10026, Yang, A. S., and Honig, B. (2019). 15, 786801. J. Mol. Chem. Coacervation of recombinant human tropoelastin is strongly influenced by the concentration of protein and NaCl and to a lesser extent on pH. The smallest amino acid, glycine is known to promote flexibility within local structures due to lack of steric hindrance, whereas prolines restrictive sidechain inhibits conformational sampling and disrupts the formation of prolonged secondary structures (Roberts et al., 2015). 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. doi: 10.1006/jmbi.1995.0502, Yeo, G. C., Baldock, C., Tuukkanen, A., Roessle, M., Dyksterhuis, L. B., Wise, S. G., et al. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Engineering a highly elastic human protein-based sealant for surgical applications. It has become increasingly evident that tropoelastins sequence, structure and subsequent functionality are in a delicate balance; thus, perturbations to tropoelastins sequence can have far-reaching consequences for self-assembly and the resultant architecture of elastic fibers. 410, 317323. Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). DEERFIELD, IL - Caterpillar Inc. (NYSE: CAT) today announced it will move its global headquarters to the company's existing office in Irving, Texas, from its current location in Deerfield, Illinois. J. Biol. J. Biol. However, higher resolution data were required to map out its elusive properties and performance within a hierarchical assembly (Tarakanova et al., 2018; Ozsvar et al., 2019). Nature 451, 977980. J. Biochem. Bioeng. Copyright 2021 Ozsvar, Yang, Cain, Baldock, Tarakanova and Weiss. This process is reversible and thermodynamically controlled and does not require protein cleavage. Dominant driving factors of assembly were examined, including water, temperature and domain pair orientations. A model two-component system for studying the architecture of elastin assembly in vitro. Matrix Biol. U.S.A. 84, 56805684. The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). Fluorescently labelled mesenchymal stem cells growing on tropoelastin. Fazio, M. J., Olsen, D. R., Kuivaniemi, H., Chu, M. L., Davidson, J. M., Rosenbloom, J., et al. Biopolymers 29, 16991706. This deduction has been corroborated by the observation that tropoelastin with multiple allysine modifications displays conformational sampling comparable to that of the wild-type molecule, suggesting it is more likely to readily participate in self-assembly. (1983). 589(19 Pt A), 24772486. doi: 10.1016/j.ajhg.2009.09.013. Below the coil is a flexible hinge region made up of domains 2024, which are directly adjacent to the bridge regions of domains 2526. Biochemistry 37, 1461314622. Sci. The tropoelastin that Elastagen manufactures is an identical copy of what naturally occurs in human tissue, meaning the clinical application opportunities for this has tremendous potential . Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). Injectable biomaterial compositions formed from tropoelastin for tissue repair and restoration. Detailed Description: doi: 10.7554/eLife.26526. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. Chem. Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. (2019b). FEBS J. Collapse Section. Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Tropoelastin monomers undergo self-assembly upon reaching the transition temperature through the aggregation of their hydrophobic domains (Wise et al., 2014). 284, 22162230. Hydrophobic domains of human tropoelastin interact in a context-dependent manner. 286, 35943610. 29, 152159. Molecular model of human tropoelastin and implications of associated mutations. doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017). For example, the highly flexible domains 25 that were noted to generate a twisting motion in N-terminus, were positioned beside domain 6, a relatively immobile region that may assist in stabilizing the subsequent regions. This temperature is also known as the transition temperature. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. 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. Invest. 33, 54685481. Proc. Provides infrastructure for further development and following approval to commercialize Elastagens products, SYDNEY February 7th: Elastagen Pty Limited, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced that it has entered into a definitive agreement under which Allergan, a leading global biopharmaceutical company, has agreed to acquire Elastagen for an upfront payment of US$95M plus contingent, commercial payments.. 282, 1248412491. In addition, Elastagen has received significant support from Australian Federal Government grants and the NSW State Government Medical Devices Fund (MDF). (1989). Characterization of an unusual tropoelastin with truncated C-terminus in the frog. More surprisingly, tropoelastins cross-linking domains are also capable of similar transitions between ordered and disordered structures. 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). The reduction in solvent accessible surface area of the mutant molecules suggests that the underlying mechanism for their altered self-assembly properties observed in experiments is due to less exposure of the appropriate hydrophobic domains required for coacervation. doi: 10.1074/jbc.270.30.17778, Cain, S. A., Baldock, C., Gallagher, J., Morgan, A., Bax, D. V., Weiss, A. S., et al. FASEB J. 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). (2019). For Elastagen contact: Robert Daniels, CEO +61 2 9209 4054. 38, 280291. Elastagen was one of the inaugural recipients of MDF funding in 2013 and will be the first to successfully repay the funding amount. Acta Gen. Subj. 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). Cell. Int. Coacervation characteristics of recombinant human tropoelastin. Tropoelastin is frequently described in the literature as an unstructured protein, mainly because models of elasticity invoke an element of disorder within the structure (4, 9, 10).While this concept appears to be the case at the fine, more subtle intramolecular level, chaos alone is unlikely to explain the ordered assembly of tropoelastin which culminates in the formation of organized . The lysines of domain 15 and 17 are believed to play key roles in this interaction. A., Rongish, B. J., Czirok, A., Zach, J., Little, C. D., Davis, E. C., et al. Figure 3. J. Biol. 10, 15321541. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). J. Biol. Biomaterials 127, 4960. 34, 8190. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. doi: 10.1016/j.matbio.2006.10.002, Dyksterhuis, L. B., and Weiss, A. S. (2010). Fed. Crosslinking [ edit] doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. Chem. Cell Biol. J. Clin. The Wellcome Trust Centre for Cell-Matrix Research is supported by funding from Wellcome Trust (203128/Z/16/Z). Elastin as a random-network elastomer: a mechanical and optical analysis of single elastin fibers. Tropoelastins hydrophobic domains are primarily responsible for facilitating coacervation (Tamburro et al., 1992; Miao et al., 2003; Muiznieks et al., 2003). The ability to stretch and recoil arises from the biochemical properties of elastins monomer, tropoelastin (discussed below). Tropoelastin has a defined shape in solution but paradoxically also displays a large percentage of flexible, disordered regions needed for molecular elasticity (4, 5).The tertiary structure of human tropoelastin represents an ensemble of elastic conformers (3, 6), yet occasional conserved sequence elements hint at requirements for functional demands in one or more key parts of this molecule (7 . (2021). 280, 3052630537. Microfibrils comprise multiple proteins, of which fibrillin-1 is the most common. This product is generally used in vitro as a substrate scaffold to enhance cell attachment, adherence and proliferation. Transl. Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking. The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. 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). Sci. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced that it has entered into a definitive agreement under which Allergan plc, a leading global biopharmaceutical company, has agreed to acquire Elastagen.
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