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). 293, 1510715119. Acad. 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. Elastin synthesis and fiber assembly. 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. (2013). Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. 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. doi: 10.1073/pnas.84.16.5680, Jensen, S. A., Vrhovski, B., and Weiss, A. S. (2000). Furthermore, tropoelastins hydrophobic and cross-linking domains are arranged in alternating patterns throughout the majority of the molecule, giving rise to both inter- and intra-domain level repetition. Sequence and structure determinants for the self-aggregation of recombinant polypeptides modeled after human elastin. A., Starcher, B. C., and Urry, D. W. (1974). doi: 10.1007/s004030050227, Tamburro, A. M., Bochicchio, B., and Pepe, A. (1981). Delineation of unusual features in the 5-flanking region. Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. Res. Another region of note is domain 36, which contains lysines but does not participate in cross-linking (Hedtke et al., 2019). J. The SAXS/SANS global shape of tropoelastin (Baldock et al., 2011) has been used to validate the full-atomistic computational model of tropoelastin through a geometric and topological comparison (Tarakanova et al., 2018). doi: 10.1002/chem.200305661. 33, 54685481. The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. 7:32. doi: 10.3389/fphar.2016.00032, Schmelzer, C. E. H., Heinz, A., Troilo, H., Lockhart-Cairns, M. P., Jowitt, T. A., Marchand, M. F., et al. J. Biol. 9:643110. doi: 10.3389/fbioe.2021.643110. Crucially, these simulations revealed that self-assembly starts with a nucleation event and elongation proceeds via both globular and fibrillar structures (Tarakanova et al., 2019a). into 200 nm then 12 m spherules, which eventually grow and stabilize into spherules 26 m in diameter (Clarke et al., 2006; Kozel et al., 2006; Tu and Weiss, 2010; Tu et al., 2010). Mol. Fabricating organized elastin in vascular grafts. 3:100016. doi: 10.1016/j.mtbio.2019.100016, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. 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). 3, 4 Elastin has a very low rate of turnover, so it . Matrix Biol. 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). 22, 109121. Evidence for the presence of alpha-aminoadipic acid delta-semialdehyde and its aldol condensation product. Aaron, B., and Gosline, J. J. Biochem. Biol. Tropoelastin is encoded by the ELN gene, which is present in all vertebrates except jawless fish (Chung et al., 2006). (2014). The Wellcome Trust Centre for Cell-Matrix Research is supported by funding from Wellcome Trust (203128/Z/16/Z). Proc. Model. 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. 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). Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Investig. Exp. B., Broekelmann, T. J., et al. doi: 10.1007/978-3-319-71530-8_13-1, Wen, Q., Mithieux, S. M., and Weiss, A. S. (2020). Comparative genomics of elastin: sequence analysis of a highly repetitive protein. Sequence variants of human tropoelastin affecting assembly, structural characteristics and functional properties of polymeric elastin in health and disease. A. 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). J. Biol. Proc. J. Mol. Coarse-grained model of tropoelastin self-assembly into nascent fibrils. Trifluoroethanol promotes helix formation by destabilizing backbone exposure: desolvation rather than native hydrogen bonding defines the kinetic pathway of dimeric coiled coil folding. The elasticity of organs and tissues in vertebrates is due to the presence of elastin, and an insoluble protein whose soluble monomer, tropoelastin, is enzymatically cross-linked through -amino groups of lysine residues. The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. Elastin as a random-network elastomer: a mechanical and optical analysis of single elastin fibers. Chem. Albert, E. N. (1972). 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. "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . Int. Chem. Nat. (2007). 13, 739743. Mol. 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. Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. 26, 125135. Elastagen was one of the inaugural recipients of MDF funding in 2013 and will be the first to successfully repay the funding amount. doi: 10.1203/00006450-199010000-00015, Nonaka, R., Sato, F., and Wachi, H. (2014). 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. 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. KP domains are found closer toward the N-terminus, whereas KA domains are closer to the C-terminus and include alanine tracts (Indik et al., 1987). Biol. Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. Importantly, the presence of fibrils indicates that the nanostructures formed during initial assembly contribute to the supramolecular structures that arise during both early (spherule) and later (fibril) stages of elastogenesis. Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). Eur. Tropoelastin is a low complexity protein on both primary and secondary sequence levels. J. Biol. 1862, 324334. Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes. (2020). doi: 10.1046/j.1432-1327.1998.2580001.x, Wang, Z., Liu, L., Mithieux, S. M., and Weiss, A. S. (2020). Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. (2006). Biopolymers 107:e23007. Together, these two properties can be tuned and exploited to give rise to an increasing number of novel biomaterials for tissue engineering and regenerative medicine, which have been recently reviewed elsewhere (Wang et al., 2020; Wen et al., 2020). doi: 10.1073/pnas.1014280108. No use, distribution or reproduction is permitted which does not comply with these terms. 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. The flexibility of the mid-region of the molecule was proposed to drive the overall elasticity of the resultant fibers. Soluble matrix protein is a potent modulator of mesenchymal stem cell performance. Biomaterials 127, 4960. U.S.A. 84, 56805684. Res. Elastin synthesis in arterial smooth muscle cell culture. doi: 10.1006/excr.1995.1321, Hinek, A., and Rabinovitch, M. (1994). CB gratefully acknowledges BBSRC funding (Ref: BB/R008221/1). Sci. Tropoelastin is a unique protein with biochemical and physical properties that allow it to rapidly self-assemble into fibrous structures. 26, 17001709. doi: 10.1002/bip.22663, Murata, K., and Wolf, M. (2018). A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors. doi: 10.1073/pnas.1701877114, Reichheld, S. E., Muiznieks, L. D., Lu, R., Sharpe, S., and Keeley, F. W. (2019). Elastin synthesis during perinatal lung development in the rat. Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. Thus, elastin is responsible, in great part, for the properties of elastic fibers. Biophys. Biochemistry 8, 28332837. doi: 10.1016/j.matbio.2009.07.003, Mithieux, S. M., Wise, S. G., Raftery, M. J., Starcher, B., and Weiss, A. S. (2005). Biomed. Thus, computational approaches can be considered as important means to complement wet bench experiments. In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. An electron microscopic study. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. doi: 10.1161/circimaging.117.007303, Prhashanna, A., Taylor, P. A., Qin, J., Kiick, K. L., and Jayaraman, A. 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). Tropoelastin. Multiple copies of the tropoelastin protein attach to one another and are processed to form a mature protein called elastin. Int. Elastin makes up the majority of elastic fibers and is formed by the hierarchical assembly of its monomer, tropoelastin. 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). Eng. Thermal compaction of disordered and elastin-like polypeptides: a temperature-dependent, sequence-specific coarse-grained simulation model. Earnings, adjusted for non-recurring costs, came . Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. Cellular activities are mediated through interactions between tropoelastin or EDPs and specific receptors on the cell surface. For more information, visit Elastagens website atwww.elastagen.com. Acta Histochem. Biotechnol. Acad. Biol. 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. FASEB J. 220, 312324. J. Exp. 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). 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. 278, 1849118498. Microfibrils comprise multiple proteins, of which fibrillin-1 is the most common. Dominant driving factors of assembly were examined, including water, temperature and domain pair orientations. 396, 870873. doi: 10.1172/jci115204, Sherratt, M., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P., Shuttleworth, C., et al. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. 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). doi: 10.1016/s0968-4328(99)00082-7, Tajima, S., Wachi, H., Uemura, Y., and Okamoto, K. (1997). Specific instructions are found in the Directions for Use. (2005). (2018). Transient tropoelastin nanoparticles are early-stage intermediates in the coacervation of human tropoelastin whose aggregation is facilitated by heparan sulfate and heparin decasaccharides. Characterization of the complete human elastin gene. doi: 10.1002/ajmg.1320340115, Indik, Z., Yeh, H., Ornstein-Goldstein, N., Sheppard, P., Anderson, N., Rosenbloom, J. C., et al. In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. Chem. doi: 10.1111/febs.14929, Hinderer, S., Shena, N., Ringuette, L. J., Hansmann, J., Reinhardt, D. P., Brucker, S. Y., et al. Isolation and characterization of human elastin cDNAs, and age-associated variation in elastin gene expression in cultured skin fibroblasts. J. Biol. Studies on the reduction of elastin. We are very interested in the blend of biochemistry and cell biology, as well as the tissue engineering and regenerative medicine opportunities provided by this amazing elastic protein. Fell muir lecture: collagen fibril formation in vitro and in vivo. Sci. FEBS Lett. Acad. 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: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). (1983). Sci. Chem. Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. Tropoelastin is a flexible molecule that retains its canonical shape. HS, which is present on cell surface proteoglycans (syndecans and glypicans), interacts strongly with tropoelastin (Cain et al., 2005). A., Gray, W. R., and Franzblau, C. (1973). 25, 492504. For example, the tetrafunctional cross-link, on which the model is based, is derived from porcine elastin (Brown-Augsburger et al., 1995). Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . 289, 14671477. Fibrillin-1 interactions with heparin. Acad. All authors contributed to writing and editing the review. Matrix Biol. Biochemistry 52, 77317741. Pathol. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. This content is for members only. Computational approaches have gained popularity in recent decades as their methodologies have been refined to provide accurate atomistic scale insights into molecular structure and movement (Tarakanova et al., 2018). (2019a). 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". 260, 32553258. 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,". 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). Adv. (1989). 85, 593605. Multimers may undergo further transitions, such as branching, to form spherules made of multimer aggregates (Tu et al., 2010). 286, 35943610. AW gratefully acknowledges NHMRC funding (Ref: 1195827). 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: 10.1126/sciadv.1501145, Yeo, G. C., and Weiss, A. S. (2019). doi: 10.1021/acs.biomac.8b01503, Rauscher, S., Baud, S., Miao, M., Keeley, F. W., and Poms, R. (2006). 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). Below the coil is a flexible hinge region made up of domains 2024, which are directly adjacent to the bridge regions of domains 2526. Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. 300, 13351359. Gene 154, 159166. Natl. A series of mapping studies have been recently conducted to pinpoint the locations of these cross-links (Schrader et al., 2018; Hedtke et al., 2019; Schmelzer et al., 2019) as their placements are crucial to understanding the resultant molecular orientation of tropoelastin within cross-linked elastin. (2017). The prevention of early self-aggregation in vitro is thought to be mediated by chaperone proteins (Hinek and Rabinovitch, 1994; Miao et al., 2013). (1965). Unsubstituted models are also critical to understanding self-assembly. doi: 10.1016/0005-2795(73)90368-1, Franzblau, C., Faris, B., and Papaioannou, R. (1969). 4, 508524. 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). doi: 10.1074/jbc.M507309200, Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). doi: 10.1016/j.micron.2009.11.003, Urban, Z., Hucthagowder, V., Schrmann, N., Todorovic, V., Zilberberg, L., Choi, J., et al. 278, 4855348562. Allysine modifications perturb tropoelastin structure and mobility on a local and global scale. Protein Eng. 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). Fluorescently labelled mesenchymal stem cells growing on tropoelastin. 58, 270277. Biomacromolecules 20, 11781189. 28, 379382. J. Therm. doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. J. Biol. 19:e1800250. This review focuses on recent developments that have shaped our current knowledge of elastin assembly through understanding the relationship between tropoelastins structure and function. ACS Biomater. Lab. J. Biol. Chem. 432, 57365751. doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). This phenomenon is supported by in vitro peptide studies, which note that increasing the space between PG motifs or removing prolines results in more ordered structures (Rauscher et al., 2006). doi: 10.1248/bpb.b13-00933, Ozsvar, J., Tarakanova, A., Wang, R., Buehler, M. J., and Weiss, A. S. (2019). doi: 10.1073/pnas.1215779110, Noguchi, A., Firsching, K., Kursar, J. D., and Reddy, R. (1990). Banded fibers in tropoelastin coacervates at physiological temperatures. Trifluoroethanol may form a solvent matrix for assisted hydrophobic interactions between peptide side chains. Dyn. doi: 10.1074/jbc.M107920200, Tu, Y., and Weiss, A. S. (2010). The smooth muscle cell. J. Biochem. 284, 22162230. Dissection of human tropoelastin: solution structure, dynamics and self-assembly of the exon 5 peptide. Package Size. doi: 10.1074/jbc.M004265200, Kadler, K. E. (2017). 87, 18281834. (2013). doi: 10.1016/s0934-8832(11)80057-0. doi: 10.1016/j.matbio.2006.09.011, Miao, M., Reichheld, S. E., Muiznieks, L. D., Huang, Y., and Keeley, F. W. (2013). doi: 10.1096/fj.201801860RR, Schrader, C. U., Heinz, A., Majovsky, P., Karaman Mayack, B., Brinckmann, J., Sippl, W., et al. Elastic fibers are an important component of the extracellular matrix, providing stretch, resilience, and cell interactivity to a broad range of elastic tissues. The most commonly investigated isoform contains domain 26A and lacks domain 22, and is predominantly found in elastic tissues (Indik et al., 1987; Vrhovski et al., 1997). doi: 10.1074/jbc.RA118.004322, Shapiro, S., Endicott, S., Province, M., Pierce, J., and Campbell, E. (1991). Biochemistry 45, 95189530. Similarly, a mutation model associated with cutis laxa, or loose skin disease (Hu et al., 2006), was found to exhibit higher stability compared with the wild-type molecule due to the increased longevity of its salt bridges (Hu et al., 2006; Tarakanova et al., 2018). The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). I thank my team at the University of Sydney and greatly look forward to seeing our science commercialized by Allergan.. Rep. 8, 116. 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. Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. doi: 10.1371/journal.pone.0046130, Hedtke, T., Schrader, C. U., Heinz, A., Hoehenwarter, W., Brinckmann, J., Groth, T., et al. J. Biol. Sci. Invest. Remodelling the extracellular matrix in development and disease. For Allergan, contact: Lisa Brown 1-862-261-7320, 1985 - 2023 BioSpace.com. 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. (2017). Tropoelastin massively associates during coacervation to form quantized protein spheres. On the cell surface, EBP forms a complex with protective protein/cathepsin A (PPCA) and neuraminidase-1 (Neu-1), giving rise to the ERC (Duca et al., 2007). 149, 282289. doi: 10.1016/j.str.2006.09.008, Rauscher, S., and Pomes, R. (2017). 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. Poly (Val-Gly-Gly-Leu-Gly). Proc. 10, 15321541. 31, 261272. The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. 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). Bioeng. doi: 10.1074/jbc.M113.533893, Reiersen, H., and Rees, A. R. (2000). Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. Unlike other companies that use paid endorsements and questionable data, NULASTIN science is proven by 3rd party clinical evaluation. Biomacromolecules 21, 35233538. Chem. For more information, visit Allergans website atwww.Allergan.com. Modeling has been verified using wet-bench methodologies, forming a robust suite of complementary methodologies that will undoubtedly become more prevalent for exploring the assembly of biological fibers over time. doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. February 14, 2018 Michael Patrini. 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). Nature 451, 977980. Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues. Bochicchio, B., Yeo, G. C., Lee, P., Emul, D., Pepe, A., Laezza, A., et al. Front. U.S.A. 115, 73387343. Free energy determinants of secondary structure formation: I. alpha-Helices. Invest. Foster, J. Cryo-electron microscopy is a rapidly developing method and likely to contribute to structural knowledge of tropoelastin. J. Biol. 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). Natl. doi: 10.1074/jbc.M510833200, Lee, P., Bax, D. V., Bilek, M. M., and Weiss, A. S. (2014). Natl. After a period of collaboration with the Elastagen team, US biopharmaceutical giant Allergan acquired Elastagen in 2018 for over $350 million in total deal value.