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Comparative genomics of elastin: sequence analysis of a highly repetitive protein. Pediatr. 87, 18281834. doi: 10.1074/jbc.M308465200, Miao, M., Bruce, A. E., Bhanji, T., Davis, E. C., and Keeley, F. W. (2007). 1862, 324334. In addition to the RKRK sequence, domain 36 contains tropoelastins sole two cysteines and only disulfide bond. 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). 280, 4093940947. Biochemistry 52, 77317741. The elastin receptor complex: a unique matricellular receptor with high anti-tumoral potential. doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. 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). (2013). Chemistry 10, 31663176. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). Investig. The bifunctional cross-links can undergo further condensation to form tetrafunctional desmosine or isodesmosine (Partridge, 1966). Tropoelastin spherules assemble at the cell surface before deposition onto the microfibrillar scaffold in cell culture systems at physiological temperature (Kozel et al., 2006). Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. doi: 10.7554/eLife.26526. Cell Physiol. 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). Figure 2. doi: 10.1073/pnas.1801205115, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. Free energy determinants of secondary structure formation: I. alpha-Helices. I thank my team at the University of Sydney and greatly look forward to seeing our science commercialized by Allergan.. Sci. 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). Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1. Biophys. Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly. 79, 277284. 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). Elastogenic cells, such as fibroblasts (Mecham et al., 1985) and smooth muscle cells (Narayanan et al., 1976), synthesize and secrete tropoelastin. Crosslinking [ edit] 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). The alignment of the tropoelastin aggregates . Characterization of the complete human elastin gene. 252, 351365. 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. Coacervation optimally occurs at physiological temperature, however, in vitro coacervation can also occur at lower temperatures depending on experimental conditions and the choice of tropoelastin isoform or derivative (Yeo et al., 2011). Tropoelastin: a versatile, bioactive assembly module. 282, 1248412491. 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. Stages of hierarchical assembly of elastic fibers. (2005). doi: 10.1093/protein/13.11.739, Roberts, S., Dzuricky, M., and Chilkoti, A. No use, distribution or reproduction is permitted which does not comply with these terms. 10, 441454. doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. (2019). Tropoelastins hydrophobic domains are primarily responsible for facilitating coacervation (Tamburro et al., 1992; Miao et al., 2003; Muiznieks et al., 2003). 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 . Elastin biomaterials in dermal repair. doi: 10.1016/j.bbagen.2017.07.020, Myers, B., Dubick, M., Last, J. Remodelling the extracellular matrix in development and disease. Binding of EDPs to the ERC induces a number of biological effects including migration, adhesion, proliferation, protease expression, and secretion. 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. 120, 419426. Biol. 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. Model. With the acquisition, Allergan will begin developing a new line that incorporates tropoelastin in the injectable's formula. Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. Elastagens revolutionary technology is based on recombinant human tropoelastin, the precursor of elastin which is a key component of youthful skin. Tropoelastin is a unique protein with biochemical and physical properties that allow it to rapidly self-assemble into fibrous structures. Dominant driving factors of assembly were examined, including water, temperature and domain pair orientations. 9:eaai7466. Arch. Visconti, R. P., Barth, J. L., Keeley, F. W., and Little, C. D. (2003). We are making enrolling in text alerts easier than ever. This temperature is also known as the transition temperature. Integrins are a major class of cell surface receptor family, of which tropoelastin has been found to interact with two types: v3 (Rodgers and Weiss, 2004) and v5. FASEB J. (2005). doi: 10.1016/s0934-8832(11)80057-0. 266, 308314. 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). 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). Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. doi: 10.1002/bip.23007, Miao, M., Stahl, R. J., Petersen, L. F., Reintsch, W. E., Davis, E. C., and Keeley, F. W. (2009). LOX and LOXL convert the -amino group of lysine to -aminoadipic acid -semialdehyde (allysine) (Schmelzer et al., 2019), which spontaneously undergo either a Schiff base reaction with a lysine, or two allysines crosslink through aldol condensation, to give rise to bifunctional crosslinks (Franzblau et al., 1969; Lent et al., 1969). Exp. 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). 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. The smooth muscle cell. (2019a). 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). 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. Coacervation involves the agglomeration of protein molecules, which is an . Assembly proceeds from a nucleation event and undergoes elongation in a step-wise manner to form a multimer which can occur in a head-to-tail fashion (Wise et al., 2014). 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 . doi: 10.1073/pnas.1215779110, Noguchi, A., Firsching, K., Kursar, J. D., and Reddy, R. (1990). 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. 37, 698702. 3:100016. doi: 10.1016/j.mtbio.2019.100016, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. Biochim. doi: 10.1002/mabi.201800250, Tiedemann, K., Batge, B., Muller, P. K., and Reinhardt, D. P. (2001). Elastin is heterogeneously cross-linked. doi: 10.1074/jbc.M510833200, Lee, P., Bax, D. V., Bilek, M. M., and Weiss, A. S. (2014). (2018). J. Pathol. (2009). Elastin: molecular description and function. 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). The ability to stretch and recoil arises from the biochemical properties of elastins monomer, tropoelastin (discussed below). J. Biol. 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. Sequence variants of human tropoelastin affecting assembly, structural characteristics and functional properties of polymeric elastin in health and disease. These interactions trigger a wide range of processes including wound healing, elastogenesis and maintenance of stemness (Yeo and Weiss, 2019). (2018). Int. Delineation of unusual features in the 5-flanking region. Reichheld, S. E., Muiznieks, L. D., Keeley, F. W., and Sharpe, S. (2017). 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). doi: 10.1073/pnas.1111615108, Yeo, G. C., Baldock, C., Wise, S. G., and Weiss, A. S. (2017). Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. doi: 10.1073/pnas.1812951116, Yue, K., Li, X., Schrobback, K., Sheikhi, A., Annabi, N., Leijten, J., et al. Received: 17 December 2020; Accepted: 08 February 2021;Published: 25 February 2021. Vallet, S. D., Miele, A. E., Uciechowska-Kaczmarzyk, U., Liwo, A., Duclos, B., Samsonov, S. A., et al. Elastagens revolutionary recombinant human tropoelastin, is identical to that present in human tissue and has many clinical applications, including effective breakthrough treatments for acne scars, stretch marks, aesthetic skin repair and wound repair. Sci. 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. 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. Biomaterials 127, 4960. (2011). 284, 22162230. Coacervation is an endothermic, entropically favorable process through which tropoelastin monomers self-assemble into higher order n-mer structures. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). It's a major component of tissues in your body that require stretchiness, like your lungs, bladder, large blood vessels and some ligaments.