tropoelastin allergan

Trends Biotechnol. doi: 10.1016/s0934-8832(11)80057-0. Unsubstituted models are also critical to understanding self-assembly. Matrix Biol. Differential expression of two tropoelastin genes in zebrafish. doi: 10.1073/pnas.1812951116, Yue, K., Li, X., Schrobback, K., Sheikhi, A., Annabi, N., Leijten, J., et al. The majority of tropoelastin synthesis occurs during perinatal development (Myers et al., 1983; Noguchi et al., 1990), however, synthesis may be triggered in response to tissue damage (Parks et al., 1992) or during diseases such as atherosclerosis (Phinikaridou et al., 2018). doi: 10.1016/j.ajhg.2009.09.013. Elastic fibers are present in the extracellular matrix (ECM) of vertebrate tissues, such as the skin, lungs, cardiovascular system, cartilage, and tendons. Tropoelastin is a low complexity protein on both primary and secondary sequence levels. Sci. Chem. Possible role in nucleated assembly. 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. Matrix Biol. Characterization of an unusual tropoelastin with truncated C-terminus in the frog. Polymorphisms in the human tropoelastin gene modify in vitro self-assembly and mechanical properties of elastin-like polypeptides. Trends towards maximal association are apparent when each of these parameters is varied. Elastagen is an exciting clinical-stage company with an advanced tissue repair platform based on tropoelastin. Allergan is an industry leader in Open Science,a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. J. Biochem. Biophys. doi: 10.1172/jci115204, Sherratt, M., Wess, T. J., Baldock, C., Ashworth, J., Purslow, P., Shuttleworth, C., et al. 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). doi: 10.1111/j.1432-1033.1997.00092.x, Vrhovski, B., and Weiss, A. S. (1998). Glycosaminoglycans (GAGs) are negatively charged, linear polysaccharides, which can be either sulfated [heparan sulfate (HS) or chondroitin sulfate] or non-sulfated (hyaluronic acid). Tropoelastin is a flexible molecule that retains its canonical shape. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. FEBS Lett. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. Biopolymers 103, 563573. Chem. Total synthesis and expression in Escherichia coli of a gene encoding human tropoelastin. Pharmacol. Sci. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. 9:643110. doi: 10.3389/fbioe.2021.643110. J. Biol. 26, 17001709. Initially, in vitro coacervation is characterized by the rapid aggregation of tropoelastin. 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). 85, 593605. For many years it was difficult to study tropoelastin at an atomic scale, but the application of computational methods, such as full-atomistic molecular dynamics and elastic network models, in combination with powerful low-resolution structural studies, have expanded the field and delivered an enhanced understanding of the mechanisms that contribute to self-assembly. February 14, 2018 Michael Patrini. (2018). The alignment of these three domains indicates that at least two tropoelastin molecules are required to form this tetrafunctional cross-link, thus, giving rise to the head-to-tail model of assembly involving the growth of a linear chain that can assemble laterally to form sheets and eventually form spherules (Baldock et al., 2011). Molecular model for elastin structure and function. The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. doi: 10.1016/j.jmb.2020.08.023, Luan, C. H., Harris, R., Prasad, K. U., and Urry, D. W. (1990). 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). Chemistry 10, 31663176. J. Tropoelastins domains each arise from single exons of the ELN gene. Dermatol. (1989). Earnings, adjusted for non-recurring costs, came . Tropoelastins sequence and domain arrangement. Med. Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Pathol. 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. This reflects the experimentally observed heterogeneity of cross-links in mature elastin, again giving weight to the hypothesis that the flexibility of tropoelastin is imperative for assembly (Schrader et al., 2018; Tarakanova et al., 2019a). Hydrophobic domains of human tropoelastin interact in a context-dependent manner. The first is an intracellular role as a tropoelastin chaperone and the second is as part of the elastin receptor complex (ERC). Nature 437, 9991002. Remarkably, optimal coacervation is found at 37 degrees C, 150 mM NaCl and pH 7-8. J. Exp. doi: 10.1006/jmbi.2000.3901, Baldock, C., Oberhauser, A. F., Ma, L., Lammie, D., Siegler, V., Mithieux, S. M., et al. 37, 698702. 41, 494497. doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. The N-terminal head caps an extended coil region that consists of domains 2-18. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Matrix Biol. Elastin is a critical skin protein consisting of crosslinked tropoelastin. J. Biol. 31, 261272. Another region of note is domain 36, which contains lysines but does not participate in cross-linking (Hedtke et al., 2019). Chem. Such models could be used in conjunction with the full molecular model of tropoelastin to examine the self-assembly of discrete regions to understand the impacts of amino acid substitutions in disease. Banded fibers in tropoelastin coacervates at physiological temperatures. Chem. All authors contributed to writing and editing the review. doi: 10.1007/978-1-4684-9093-0_25, Scandolera, A., Odoul, L., Salesse, S., Guillot, A., Blaise, S., Kawecki, C., et al. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. Isolation and characterization of crosslinked peptides from elastin. (2015). Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). Int. Biochimie 86, 173178. Mol. Powered by Madgex Job Board Software. 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. Ann. For example, the tetrafunctional cross-link, on which the model is based, is derived from porcine elastin (Brown-Augsburger et al., 1995). Biochemistry 36, 84138421. Cell Biol. Elastic fibers are composed of approximately 90% elastin, whilst the remaining components are primarily comprised of fibrillin glycoproteins (Mecham, 1991). 286, 35943610. Calorim. Acad. The advantage of coarse-grained methodologies is that they allow for the simulation of timescales of large molecular systems on the order of microseconds, which are otherwise computationally infeasible with classical full-atomistic molecular dynamics. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. Natl. The most crucial of these properties is the ability to undergo many stretch-recoil cycles whilst maintaining the structural and functional integrity of elastic tissues over an organisms lifetime. doi: 10.1021/bi060289i, Tarakanova, A., and Buehler, M. J. Chem. doi: 10.1016/0378-1119(94)00848-m, McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. The process of tropoelastin aggregation is initially reversible, as spherules dissipate if the temperature is lowered (Clarke et al., 2006), however, maintenance of a physiological temperature results in maturation, which is indicated by spherule coalescence and the irreversible formation of fibrillar structures (Cox et al., 1974; Bressan et al., 1983; Mithieux et al., 2005). (2012). In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. 22, 109121. doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). Implications for microfibril and elastic fiber assembly. (1995). Am. 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). 150, 154162. doi: 10.1016/j.matbio.2006.09.011, Miao, M., Reichheld, S. E., Muiznieks, L. D., Huang, Y., and Keeley, F. W. (2013). It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments. Coacervation of recombinant human tropoelastin is strongly influenced by the concentration of protein and NaCl and to a lesser extent on pH. Biopolymers 20, 12471260. J. Biol. Partridge, S. M. (1966). Dissection of human tropoelastin: exon-by-exon chemical synthesis and related conformational studies. doi: 10.1073/pnas.1014280108. Adv. Thus, elastin is responsible, in great part, for the properties of elastic fibers. 9:eaai7466. Trends Biotechnol. Biol. Dissection of human tropoelastin: solution structure, dynamics and self-assembly of the exon 5 peptide. Chem. Molecular modeling of protein materials: case study of elastin. (2017). Macromol. Genet. doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). Water structure and elastin-like peptide aggregation. Figure 1. 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). The ability to stretch and recoil arises from the biochemical properties of elastins monomer, tropoelastin (discussed below). 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). 10, 441454. 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. 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). Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. Biochemistry 8, 28372845. Genet. Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. U.S.A. 116, 20422051. 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. Engineering a highly elastic human protein-based sealant for surgical applications. On a per-share basis, the Irving, Texas-based company said it had profit of 1 cent. Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain. Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1. doi: 10.1016/0014-4800(65)90015-8, He, D., Chung, M., Chan, E., Alleyne, T., Ha, K. C. H., Miao, M., et al. doi: 10.1021/bi400760f, Miao, M., Reichheld, S. E., Muiznieks, L. D., Sitarz, E. E., Sharpe, S., and Keeley, F. W. (2017). Reichheld, S. E., Muiznieks, L. D., Keeley, F. W., and Sharpe, S. (2017). (2017). A., Ishibashi, H., Werneck, C. C., Keeley, F. W., Zhang, L., et al. doi: 10.1016/j.febslet.2015.08.029, Rodgers, U. R., and Weiss, A. S. (2004). doi: 10.1073/pnas.1215779110, Noguchi, A., Firsching, K., Kursar, J. D., and Reddy, R. (1990). 432, 57365751. 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). Synthesis and structural studies of a pentapeptide sequence of elastin. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. 68, 411419. J. Hum. Matrix Biol. Tropoelastin is an ECM component primarily located in elastic tissues and has been shown to promote the expansion of hematopoietic stem cells (HSCs) and MSCs when used as a substrate coating or as part of the substrate bulk material ().The ECM is proposed to modulate stem cell phenotype and activity, including proliferation, via its chemistry, topography, and mechanical properties (). doi: 10.1161/circimaging.117.007303, Prhashanna, A., Taylor, P. A., Qin, J., Kiick, K. L., and Jayaraman, A. 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). 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. Coacervation characteristics of recombinant human tropoelastin. Chem. Collapse Section. EBP plays two roles in the assembly of elastin. (2006). 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). 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. doi: 10.1111/iep.12224, Kentsis, A., and Sosnick, T. R. (1998). These ordered structures can include -helices and -structures (Vrhovski et al., 1997), which depend on the amino acid content and arrangement of domains (He et al., 2012; Reichheld et al., 2014, 2017; Muiznieks et al., 2015) and the choice of solvent (Reiersen and Rees, 2000; Muiznieks et al., 2015). J. Biochem. Invest. (2013). 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. doi: 10.1007/978-3-319-71530-8_13-1, Wen, Q., Mithieux, S. M., and Weiss, A. S. (2020). Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). Structure 14, 16671676. Indeed, cryo-EM was recently reported to have a lower molecular size limit of approximately 50 kDa, however, it has not yet been successfully applied to characterize tropoelastin (Murata and Wolf, 2018). 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). (2011). A comprehensive map of human elastin cross-linking during elastogenesis. 28, 379382. Eur. A., Starcher, B. C., and Urry, D. W. (1974). Elastin is highly hydrophobic, extensively cross-linked, and is assembled into elastic fibers in a dynamic process involving cells, cell surface receptors, and numerous elastic fiber . Human ELN gives rise to a broad variety of splice isoforms, with alternative splicing being observed with exons 22, 23, 24, 26A, 32, and 33 (Fazio et al., 1988; Parks et al., 1992) that result in 13 known human isoforms of the mature tropoelastin protein (Reichheld et al., 2019). 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). Sci. Reichheld, S. E., Muiznieks, L. D., Huynh, Q., Wang, N., Ing, C., Miao, M., et al. 293, 1510715119. Cellular expression of tropoelastin mRNA splice variants. Cell Physiol. doi: 10.1074/jbc.270.30.17778, Cain, S. A., Baldock, C., Gallagher, J., Morgan, A., Bax, D. V., Weiss, A. S., 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. (1965). Commun. doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. J. Mol. Binding of EDPs to the ERC induces a number of biological effects including migration, adhesion, proliferation, protease expression, and secretion. Protein Eng. Biochemistry 42, 1334713362. Detailed Description: Sci. 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.