J. Clin. 10 Endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts produce tropoelastin during the late 270, 1777817783. 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). Implications for microfibril and elastic fiber assembly. Allergan Highlights Key Growth Drivers for Medical Aesthetics doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. The conserved C-terminus is an area of the molecule of particular biological importance in that it is required for both incorporation into elastin and for cellular interactions. J. Biol. doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. Acta 303, 363369. U.S.A. 84, 56805684. Biochemistry 37, 1461314622. Chem. 289, 1005710068. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). Dermatol. doi: 10.1021/acs.biomac.6b01759, Mackay, J. P., Muiznieks, L. D., Toonkool, P., and Weiss, A. S. (2005). Adv. Figure 3. 149, 282289. Form. (1973). (2020). Fluorescently labelled mesenchymal stem cells growing on tropoelastin. (2006). Modulative effects are also observed within full length tropoelastin, where disruptions to domain 26 diminish self-assembly (Jensen et al., 2000), highlighting the context of primary sequence on higher order structures. Simul. (2001). This review focuses on recent developments that have shaped our current knowledge of elastin assembly through understanding the relationship between tropoelastins structure and function. For this injection, the researchers used a new . Trends Biotechnol. Localizing alpha-helices in human tropoelastin: assembly of the elastin puzzle. (2013). doi: 10.1021/bi034837t, Tamburro, A. M., Guantieri, V., and Gordini, D. D. (1992). Fazio, M. J., Olsen, D. R., Kuivaniemi, H., Chu, M. L., Davidson, J. M., Rosenbloom, J., et al. The Weiss Lab's research focuses on the use of human tropoelastin in tissue assembly and wound repair. 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. 19:e1800250. (2021). 280, 4093940947. (1995). Tropoelastin - an overview | ScienceDirect Topics 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). 289, 14671477. Genet. Elastagen is creating injectables using recombinant human tropelastin, a substance that's crucial for producing elastin fibers in the skin. Biomacromolecules 18, 599609. Shape of tropoelastin, the highly extensible protein that - PNAS (1995). 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). Mol. Our understanding of key aspects of the assembly process have been unclear due to the intrinsic properties of elastin and tropoelastin that render them difficult to study. Tropoelastin, the soluble precursor to elastin, and the degradation products of fragmented elastic fibers also have important chemical signaling properties. 293, 1510715119. 26, 115124. doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. Identification of an elastin cross-linking domain that joins three peptide chains. EDPs can modulate an array of signal pathways (Scandolera et al., 2016), but full-length tropoelastin does not trigger pathways through the ERC. Biochemistry 8, 28372845. 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. 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). Scientists find way to heal scars left behind by heart attacks The authors wrote and submitted this manuscript in response to an invitation by the Editor. Int. Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. Evidence for the presence of alpha-aminoadipic acid delta-semialdehyde and its aldol condensation product. (2019a). 276, 4457544580. Biophys. 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. Comparative genomics of elastin: sequence analysis of a highly repetitive protein. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. 85, 593605. Aaron, B., and Gosline, J. U.S.A. 110, 28522857. We are making enrolling in text alerts easier than ever. 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). Matrix 12, 156162. (1989). 10:034102. doi: 10.1088/1748-6041/10/3/034102, Hinek, A., Keeley, F. W., and Callahan, J. 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. The conversion of a single lysine to an allysine results in structural stabilization, which may serve as a checkpoint during self-assembly to ensure that molecules incapable of forming multiple cross-links are not incorporated into the growing chain. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. 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. Biomacromolecules 20, 11781189. Bochicchio, B., Yeo, G. C., Lee, P., Emul, D., Pepe, A., Laezza, A., et al. doi: 10.1016/j.bbrc.2010.05.013, Elvin, C. M., Carr, A. G., Huson, M. G., Maxwell, J. M., Pearson, R. D., Vuocolo, T., et al. J. Biol. 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). 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. doi: 10.1073/pnas.1801205115, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. Pharm. (2006). Remarkably, optimal coacervation is found at 37 degrees C, 150 mM NaCl and pH 7-8. Tropoelastin promotes cell attachment and migration of several cell types including fibroblasts, endothelial cells and mesenchymal stem cells. The next stage of elastin assembly involves the deposition of tropoelastin spherules onto the microfibril scaffold of elastic fibers. doi: 10.1016/j.biochi.2004.03.002, Sandberg, L. B., Gray, W. R., Foster, J. doi: 10.1074/jbc.M113.518381, Lee, P., Yeo, G. C., and Weiss, A. S. (2017). 25, 10231029. Elastin - Wikipedia Trends Biotechnol. doi: 10.1021/bi00835a021, Gray, W. R., Sandberg, L. B., and Foster, J. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced. doi: 10.1007/s10973-014-4254-9, Debelle, L., and Tamburro, A. M. (1999). Acad. A new amino acid from hydrolysates of elastin. U.S.A. 109, 28782883. 22, 109121. Matrix Biol. Cell Res. III. Natl. Chem. 84, 6880. 278, 1849118498. Am. February 14, 2018 Michael Patrini. U.S.A. 116, 20422051. Med. doi: 10.1046/j.1432-1327.1998.2580001.x, Wang, Z., Liu, L., Mithieux, S. M., and Weiss, A. S. (2020). doi: 10.1002/bip.23007, Miao, M., Stahl, R. J., Petersen, L. F., Reintsch, W. E., Davis, E. C., and Keeley, F. W. (2009). Sci. Coacervation characteristics of recombinant human tropoelastin (2019). Structural changes and facilitated association of tropoelastin. The company is particularly pointing to usage in the treatment of acne scars, stretch marks, aesthetic skin repair and surgical wound repair. A., Starcher, B. C., and Urry, D. W. (1974). The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. A Study to Evaluate the Efficacy of ELAPR002f in Females and Males With 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. The hydrophobic domains have been extensively studied and are responsible for facilitating tropoelastins ability to self-assemble (Vrhovski et al., 1997; Toonkool et al., 2001). doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017). Molecular model for elastin structure and function. doi: 10.1111/iep.12224, Kentsis, A., and Sosnick, T. R. (1998). (1965). Biopolymers [Epub ahead of print]. Effect of peptide sequence on the LCST-like transition of elastin-like peptides and elastin-like peptidecollagen-like peptide conjugates: simulations and experiments. 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). Proc. Differential expression of two tropoelastin genes in zebrafish. Acta Gen. Subj. The ability to stretch and recoil arises from the biochemical properties of elastins monomer, tropoelastin (discussed below). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Biophys. (2011). Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. A., Wachi, H., Davis, E. C., and Mecham, R. P. (2003). 26, 524540. The hydrophobic domain 26 of human tropoelastin is unstructured in solution. 1862, 324334. Molecular model of human tropoelastin and implications of associated mutations. Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. doi: 10.1007/978-3-319-71530-8_13-1, Wen, Q., Mithieux, S. M., and Weiss, A. S. (2020). A. Institute of Polymers, Composites and Biomaterials, National Research Council (IPCB-CNR), Italy, Washington University in St. Louis, United States. The coacervate is made insoluble by irreversible crosslinking. 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. doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. Exp. 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. (1981). 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). Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues. Production of recombinant human tropoelastin: Characterization and Acta Biomater. J. Therm. Allysine modifications perturb tropoelastin structure and mobility on a local and global scale. Proc. Cell Biol. Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie .

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