tropoelastin allergan
Am. Arch. Instead, tropoelastin domains 1418 and 36 (RKRK sequence) have been found to bind to both integrins. Allergan to acquire University of Sydney spinoff Elastagen In addition to its involvement in molecular elasticity, the flexibility of tropoelastin also a key requirement for self-assembly into elastin, with mutations that perturb this having detrimental effects on tissue (Yeo et al., 2016, 2017). Tropoelastin promotes cell attachment and migration of several cell types including fibroblasts, endothelial cells and mesenchymal stem cells. doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). J. Hum. (2015). Clinical Relevance of Elastin in the Structure and Function of Skin Hogan Lovells represented Elastagen Pty Ltd. on the deal. 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. Cryo-electron microscopy for structural analysis of dynamic biological macromolecules. 207, 8796. Protein Eng. Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. Thermal compaction of disordered and elastin-like polypeptides: a temperature-dependent, sequence-specific coarse-grained simulation model. Engineering a highly elastic human protein-based sealant for surgical applications. Anal. 280, 3052630537. Biopolymers 107:e23007. Forty tropoelastin molecules were subjected to simulations using a MARTINI-based coarse-grained model, integrated with an elastic network model (Tarakanova et al., 2019a). Molecular model for elastin structure and function. While the clinical stage tropoelastin platform provides multiple opportunities for aesthetics, scar remodelling and tissue repair, it also has the . For Allergan, contact: Lisa Brown 1-862-261-7320, 1985 - 2023 BioSpace.com. 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. 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. Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. (1973). Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. With the acquisition, Allergan will begin developing a new line that incorporates tropoelastin in the injectable's formula. doi: 10.1016/j.tibtech.2019.08.005, Wise, S. G., and Weiss, A. S. (2009). doi: 10.1002/mabi.201800250, Tiedemann, K., Batge, B., Muller, P. K., and Reinhardt, D. P. (2001). Proc. The business could generate net sales of approximately $7 to $8 billion in 2025 from $3.8 billion in 2017. Trends Biotechnol. Advanced BioMatrix - Recombinant Tropoelastin, Lyophilized #5052 1862, 324334. Biochim. Coacervation characteristics of recombinant human tropoelastin. 27, 441450. 26, 17001709. (1981). 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. (2019b). Acad. 28, 432441. Biochim. doi: 10.1111/j.1432-1033.1997.00092.x, Vrhovski, B., and Weiss, A. S. (1998). (2017). Arch. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. Am. Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. 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]. Res. Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry. doi: 10.1111/febs.14929, Hinderer, S., Shena, N., Ringuette, L. J., Hansmann, J., Reinhardt, D. P., Brucker, S. Y., et al. KA domains were initially thought to form -helices and poly-proline II helices (PPII) due to the presence of cross-links which require a lysine arrangement that was postulated to be achieved via -helical configuration (Brown-Augsburger et al., 1995). doi: 10.1074/jbc.270.30.17778, Cain, S. A., Baldock, C., Gallagher, J., Morgan, A., Bax, D. V., Weiss, A. S., et al. Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. 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. 149, 282289. doi: 10.1016/0378-1119(94)00848-m, McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. Tropoelastin: a novel marker for plaque progression and instability. (2006). Tropoelastin - an overview | ScienceDirect Topics Acad. Healthcare Investment Banking - The Walden Group Intracellularly, EBP is associated with tropoelastin after the release of the signal peptide and acts as a chaperone to prevent self-aggregation and proteolysis as it transported to the cell membrane, after which EBP is then recycled and serves as a reusable shuttle protein (Hinek et al., 1995). doi: 10.1016/s0945-053x(03)00014-3, Vrhovski, B., Jensen, S., and Weiss, A. S. (1997). 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. 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. 41, 494497. 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. 252, 351365. The computational model uncovered the contributions of each molecular region to the flexibility of the molecule. J. Biol. 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. Overview of the computational and experimental methodologies that have recently contributed to our understanding of elastic fiber assembly. Mol. doi: 10.1021/bi034837t, Tamburro, A. M., Guantieri, V., and Gordini, D. D. (1992). Although there is no 3D structure for porcine tropoelastin, porcine tropoelastin differs from that of humans (Sandberg et al., 1977), leaving it unclear as to whether these domains align as expected in human tissue. N. Y. Acad. Chem. Today Biol. (1995). Nature 246, 461466. 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). The liquid structure of elastin. Mater. Biochemistry 42, 1334713362. 21:063001. doi: 10.1088/0965-0393/21/6/063001, Tarakanova, A., Huang, W., Weiss, A. S., Kaplan, D. L., and Buehler, M. J. 10 Endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts produce tropoelastin during the late Int. 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). 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. Thus, elastin is responsible, in great part, for the properties of elastic fibers. Coarse-grained model of tropoelastin self-assembly into nascent fibrils. The lysines of domain 15 and 17 are believed to play key roles in this interaction. 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). (2006). Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin. 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). 300, 13351359. Biopolymers [Epub ahead of print]. Transglutaminase-mediated cross-linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. 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). 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). Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. (2007). doi: 10.1016/j.ajhg.2009.09.013. doi: 10.1002/jcp.20546, Kozel, B. J. Biol. 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). Coacervation characteristics of recombinant human tropoelastin Coacervation of tropoelastin. (2011). Collapse Section. Tropoelastins hydrophobic domains are primarily responsible for facilitating coacervation (Tamburro et al., 1992; Miao et al., 2003; Muiznieks et al., 2003). 293, 1510715119. Frontiers | Tropoelastin and Elastin Assembly doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). Fabricating organized elastin in vascular grafts. Differential expression of two tropoelastin genes in zebrafish. Cell Biol. 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). Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. 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. doi: 10.1074/jbc.M308465200, Miao, M., Bruce, A. E., Bhanji, T., Davis, E. C., and Keeley, F. W. (2007). doi: 10.1021/acsbiomaterials.6b00564, Yeo, G. C., Keeley, F. W., and Weiss, A. S. (2011). Allergan announced that it would be accessing Elastagen's next generation Juvederm dermal filler injectable portfolio, which will now also boast its "key 'youth protein' tropoelastin". Structural analysis of photocrosslinkable methacryloyl-modified protein derivatives. 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). doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. Biochemistry 52, 77317741. 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). Int. PLoS One 7:e46130. doi: 10.1021/acs.biomac.8b01503, Rauscher, S., Baud, S., Miao, M., Keeley, F. W., and Poms, R. (2006). Form. Powered by Madgex Job Board Software. doi: 10.1038/nature06669, Cox, B. Sci. Furthermore, the SAXS/SANS structure has been mapped to an elastic network model with tunable stiffness to probe the role of tropoelastins flexibility in fiber assembly (Yeo et al., 2016). doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. Am. They are ubiquitous across most vertebrates other than lower vertebrates such as species from the superclass Agnatha (jawless fish) (Debelle and Tamburro, 1999). doi: 10.1006/excr.1995.1321, Hinek, A., and Rabinovitch, M. (1994). Biochemistry 36, 84138421. 37, 698702. Biol. (2013). The hydrophobic domains contain aliphatic amino acids with proline variations that provide flexibility and the ability to assemble into higher order structures. Chem. doi: 10.7554/eLife.26526. 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. Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. Figure 1. Exp. FEBS J. 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). (2021). Allergan's Acquisition of Elastagen. 589(19 Pt A), 24772486. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. Primary structure of porcine tropoelastin. 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). Chemistry 10, 31663176. Implications for tissue specificity and durability of elastic tissue. [Epub ahead of print]. Identification of an elastin cross-linking domain that joins three peptide chains. 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. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. Tropoelastin #5052. 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. 264, 88878891. Shape of tropoelastin, the highly extensible protein that - PNAS 29, 152159. This product is generally used in vitro as a substrate scaffold to enhance cell attachment, adherence and proliferation. The coacervate is made insoluble by irreversible crosslinking. (1995). The N-terminal head caps an extended coil region that consists of domains 218. 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. Domain 36 of tropoelastin in elastic fiber formation. Eng. Allergans success is powered by our global colleagues commitment to being Bold for Life. Biomed. Elastin-like polypeptides as models of intrinsically disordered proteins. 280, 4093940947. Acad. 25, 492504. J. Mol. Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. J. Struct. Exp. 275, 2844928454. 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). 3, 28322844. For example, their inclusion in peptides derived from hydrophobic domains confers decreased times taken for self-assembly, most likely due to their favorable interaction with aqueous solvent (Miao et al., 2003). Patient Homepage | Accredo Matrix Biol. 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).
