tropoelastin allergan

III. 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. Chem. 69, 89102. Crosslinking [ edit] doi: 10.1161/circimaging.117.007303, Prhashanna, A., Taylor, P. A., Qin, J., Kiick, K. L., and Jayaraman, A. Allergan Snaps Up Sydney Biotech for Upfront Payment of US $95M Proc. Elastogenesis in human aorta: an electron microscopic study. 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. 43, 131138. 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). Exp. 38, 280291. 84, 6880. doi: 10.1248/bpb.b13-00933, Ozsvar, J., Tarakanova, A., Wang, R., Buehler, M. J., and Weiss, A. S. (2019). Res. Characterization of the complete human elastin gene. The ELN gene provides instructions for making a protein called tropoelastin. Chem. J. Biol. Fed. 300, 13351359. J. Biochem. Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. Trifluoroethanol may form a solvent matrix for assisted hydrophobic interactions between peptide side chains. doi: 10.1074/jbc.M510833200, Lee, P., Bax, D. V., Bilek, M. M., and Weiss, A. S. (2014). Elastin, arterial mechanics, and cardiovascular disease The hydrophobic domains contain repetitions and variations of Val-Pro-Gly-Val-Gly motifs (Figure 1), resulting in the aforementioned low complexity of sequence (Foster et al., 1973; Gray et al., 1973). 16,17 We have previously shown that monomeric TE is utilized as a substrate by dermal fibroblasts in the formation of elastin fibroblasts in vitro, where Cooperativity between the hydrophobic and cross-linking domains of elastin. 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. Natl. FASEB J. Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin. Elastin binding protein (EBP) is a splice variant of -galactosidase, that recognizes the repetitive hydrophobic sequences (VGVAPG) of tropoelastin (Tajima et al., 1997). doi: 10.1016/j.actbio.2013.08.003, Wu, W. J., and Weiss, A. S. (1999). Vallet, S. D., Miele, A. E., Uciechowska-Kaczmarzyk, U., Liwo, A., Duclos, B., Samsonov, S. A., et al. doi: 10.1083/jcb.126.2.563, Hu, Q., Reymond, J. L., Pinel, N., Zabot, M. T., and Urban, Z. 410, 317323. 264, 88878891. Natl. Baul, U., Bley, M., and Dzubiella, J. An electron microscopic study. (2020). Patient Homepage | Accredo Water structure and elastin-like peptide aggregation. doi: 10.1002/chem.200305661. (2013). Latent TGF- binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Cell Physiol. Biochimie 86, 173178. Mol. Elastagens revolutionary technology is based on recombinant human tropoelastin, the precursor of elastin which is a key component of youthful skin. 258, 118. doi: 10.1016/s0968-4328(99)00082-7, Tajima, S., Wachi, H., Uemura, Y., and Okamoto, K. (1997). Cross-linking requires the modification of at least one of the lysine participants by a member of the copper-containing LOX or lysine oxidase-like (LOXL) enzyme families. FEBS J. doi: 10.1074/jbc.M308465200, Miao, M., Bruce, A. E., Bhanji, T., Davis, E. C., and Keeley, F. W. (2007). Elastins subunit, tropoelastin, is a soluble 6070 kDa protein which has been intensely studied over the past three decades. Of most importance, the inability to acquire large quantities of pure tropoelastin historically presented a significant obstacle to experimentally characterizing its structure. 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). US8974803B2 - Injectable biomaterials - Google Patents CB gratefully acknowledges BBSRC funding (Ref: BB/R008221/1). (2018). Ltd., which was sold to Allergan, now a division of AbbVie. 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. Future investigations will allow the bridging of the gap between mesoscale simulations and microscopically observed coacervation (Clarke et al., 2006). (2017). J. Struct. Allergan to acquire Australian biotech company Elastagen (1987). 21:063001. doi: 10.1088/0965-0393/21/6/063001, Tarakanova, A., Huang, W., Weiss, A. S., Kaplan, D. L., and Buehler, M. J. Elastic fibers provide tissues with mechanical resilience, durability, and cell interactivity, which support a diverse range of specialized functionality. Biomaterials 127, 4960. Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. Chem. Mater. Tropoelastin - PubMed 396, 870873. Dominant driving factors of assembly were examined, including water, temperature and domain pair orientations. Domain 26 of tropoelastin plays a dominant role in association by coacervation. Biophys. Possible role in nucleated assembly. Advanced BioMatrix - Recombinant Tropoelastin, Lyophilized #5052 Adv. "We believe it's in the best strategic interest of the company to make this move, which supports Caterpillar's strategy for profitable . doi: 10.1016/j.matbio.2009.10.003, Tu, Y., Wise, S. G., and Weiss, A. S. (2010). 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). Sci. (1973). Nature 437, 9991002. Sci. J. Biol. eLife 6:e26526. With the acquisition, Allergan will begin developing a new line that incorporates tropoelastin in the injectable's formula. doi: 10.1016/j.biocel.2008.03.017, Wise, S. G., Yeo, G. C., Hiob, M. A., Rnjak-Kovacina, J., Kaplan, D. L., Ng, M. K., et al. Albert, E. N. (1972). Acad. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Positively charged lysine residues in domains 17 were identified to interact with negatively charged HS, most likely via ionic interactions (Lee et al., 2017). Structure 14, 16671676. Coarse-grained model of tropoelastin self-assembly into nascent fibrils. 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). U.S.A. 115, 73387343. 266, 308314. Tropoelastin is a flexible molecule that retains its canonical shape. Fluor: Q4 Earnings Snapshot | AP News FEBS J. The alignment of the tropoelastin aggregates . Tropoelastins domains each arise from single exons of the ELN gene. doi: 10.1016/s0003-9861(02)00719-1, Muiznieks, L. D., Reichheld, S. E., Sitarz, E. E., Miao, M., and Keeley, F. W. (2015). 432, 57365751. J. Ultrastruct. Allergan acquired Elastagen primarily for the injectable product portfolio (acne scars/stretch marks aesthetics). Anal. Lyophilized Powder. Biophys. doi: 10.1074/jbc.M507309200, Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). Elastin: Structure, Function, Skin Care & Supplements - Cleveland Clinic Protein Eng. Partridge, S. M. (1966). Its hydrophobic (pink) and cross-linking (blue) domains consist of repetitive motifs that contribute uniquely to elastin assembly. Figure 2. Acta Gen. Subj. Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Thus, elastin is responsible, in great part, for the properties of elastic fibers. Thus, computational approaches can be considered as important means to complement wet bench experiments. Human tropoelastin improves rat heart function postmyocardial infarction and could potentially be used to treat heart failure. Matrix Biol. This temperature is also known as the transition temperature. Chem. Natl. J. Biol. With leaps in the improvement of cryogenic electron microscopy to characterize flexible molecules, we predict that this approach will contribute to a deeper understanding of tropoelastin structure and self-assembly in the context of endogenous fiber formation and biomaterials fabrication. Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners. 120, 419426. doi: 10.1046/j.1432-1327.1999.00891.x, Yamauchi, Y., Tsuruga, E., Nakashima, K., Sawa, Y., and Ishikawa, H. (2010). doi: 10.1074/jbc.M104985200, Toonkool, P., Jensen, S. A., Maxwell, A. L., and Weiss, A. S. (2001). doi: 10.1021/bi0610092, Cordier, P., Tournilhac, F., Souli-Ziakovic, C., and Leibler, L. (2008). 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. A model two-component system for studying the architecture of elastin assembly in vitro. Dermatol. Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues. 1, 2 Elastogenesis, the process of elastin formation, mainly occurs during the fetal and early neonatal development of organs such as blood vessels, lungs, and skin. Transglutaminase-mediated cross-linking of tropoelastin to fibrillin stabilises the elastin precursor prior to elastic fibre assembly. Acad. doi: 10.1016/s1357-2725(98)00098-3, Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., et al. 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). Tropoelastin (TE) is the main (>90%) component of elastin, wherein crosslinked assembled coacervates of TE are exposed to lysyl oxidases and interact with microfibrils to expand elastin fibers. doi: 10.1038/nrm3904, Bressan, G. M., Castellani, I., Giro, M. G., Volpin, D., Fornieri, C., and Pasquali Ronchetti, I. J. Biol. doi: 10.1021/bi00835a022, Lockhart-Cairns, M. P., Newandee, H., Thomson, J., Weiss, A. S., Baldock, C., and Tarakanova, A. Allergan Highlights Key Growth Drivers for Medical Aesthetics Forty tropoelastin molecules were subjected to simulations using a MARTINI-based coarse-grained model, integrated with an elastic network model (Tarakanova et al., 2019a). Tropoelastin is frequently described in the literature as an unstructured protein, mainly because models of elasticity invoke an element of disorder within the structure (4, 9, 10).While this concept appears to be the case at the fine, more subtle intramolecular level, chaos alone is unlikely to explain the ordered assembly of tropoelastin which culminates in the formation of organized . Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin. doi: 10.1083/jcb.68.3.411, Noda, K., Dabovic, B., Takagi, K., Inoue, T., Horiguchi, M., Hirai, M., et al. 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]. Allysine modifications perturb tropoelastin structure and mobility on a local and global scale. J. Biol. Similar to other ECM proteins, such as collagen, tropoelastin covalently cross-links via its lysines. J. Adv. J. Struct. 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). 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. 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. 1862, 324334. 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). The hydrophobic domains are involved in coacervation and the hydrophilic domains are used for cross-linking. 282, 1248412491. Coacervation of tropoelastin. 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). Biol. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, womens health, urology and anti-infectivetherapeutic categories. A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors. Background: Elastin is an essential component of the dermis, providing skin with elasticity and integrity. Sequence and structure determinants for the self-aggregation of recombinant polypeptides modeled after human elastin. (2019a). Bioeng. Elastic fibers are composed of approximately 90% elastin, whilst the remaining components are primarily comprised of fibrillin glycoproteins (Mecham, 1991). U.S.A. 112, E4408E4415. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world. doi: 10.1016/s0934-8832(11)80057-0. Acad. Annabi, N., Zhang, Y. N., Assmann, A., Sani, E. S., Cheng, G., Lassaletta, A. D., et al. The bifunctional cross-links can undergo further condensation to form tetrafunctional desmosine or isodesmosine (Partridge, 1966). doi: 10.1002/bip.22663, Murata, K., and Wolf, M. (2018). In addition, Elastagen has received significant support from Australian Federal Government grants and the NSW State Government Medical Devices Fund (MDF). 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. 26, 125135. Delineation of unusual features in the 5-flanking region. Nature 451, 977980. Tropoelastin: a versatile, bioactive assembly module - PubMed 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). (2021). J. Biochem. 79, 277284. Cytochem. The smooth muscle cell. 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). For Elastagen contact: Robert Daniels, CEO +61 2 9209 4054. Tropoelastin interacts with microfibril components including fibrillin-1, fibulin-4, and -5, and other associated molecules such as latent transforming growth factor binding protein-4 (Visconti et al., 2003; McLaughlin et al., 2006; Urban et al., 2009; Yamauchi et al., 2010; Noda et al., 2013; Lockhart-Cairns et al., 2020). Invest. (2012). Modulation by elastin peptide VGVAPG of cell proliferation and elastin expression in human skin fibroblasts. 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. CICADA TURNS 20: How synthetic skin biotech Elastagen changed lives Mechanism of helix induction by trifluoroethanol: a framework for extrapolating the helix-forming properties of peptides from trifluoroethanol/water mixtures back to water. (2005). FEBS J. Elastin synthesis in arterial smooth muscle cell culture. The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. The stiffness that arose due to amino acid substitutions partially determined resultant secondary structure which, in turn, impacted assembly (Prhashanna et al., 2019). The understanding of tropoelastins structure has been hindered by numerous intrinsic properties of the molecule. doi: 10.1128/mcb.26.5.1700-1709.2006, Mecham, R. P. (1991). ELN gene: MedlinePlus Genetics 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. Isolation and characterization of human elastin cDNAs, and age-associated variation in elastin gene expression in cultured skin fibroblasts. Biol. Chem. J. Biol. Chem. (2018). 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). FEBS Lett. Shape of tropoelastin, the highly extensible protein that - PNAS Deficient coacervation of two forms of human tropoelastin associated with supravalvular aortic stenosis. Increased cyclic GMP levels lead to a stimulation of elastin production in ligament fibroblasts that is reversed by cyclic AMP. Elastagen Pty Ltd, a clinical stage company developing medical device products based on recombinant tropoelastin, today announced. Coacervation characteristics of recombinant human tropoelastin. Tropoelastin is a low complexity protein on both primary and secondary sequence levels. 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. Chemistry 10, 31663176. 3:100016. doi: 10.1016/j.mtbio.2019.100016, Tarakanova, A., Yeo, G. C., Baldock, C., Weiss, A. S., and Buehler, M. J. Upon secretion tropoelastin has the propensity to self-aggregate through a process known as coacervation. doi: 10.1074/jbc.RA118.004322, Shapiro, S., Endicott, S., Province, M., Pierce, J., and Campbell, E. (1991). doi: 10.1006/jmbi.1995.0502, Yeo, G. C., Baldock, C., Tuukkanen, A., Roessle, M., Dyksterhuis, L. B., Wise, S. G., et al. Characterization of an unusual tropoelastin with truncated C-terminus in the frog. (2001). Multimers may undergo further transitions, such as branching, to form spherules made of multimer aggregates (Tu et al., 2010). 41, 494497. J. Biol. By probing mutations in computational studies that resolve the atomistic structure of the molecule, the deduction of mechanisms associated with changes to functional roles of specific domains has become feasible, and a connection between local structures and biological performance can be established (Figure 2; Tarakanova et al., 2018). Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: clues to the evolutionary history of elastins. Pepe, A., Flamia, R., Guerra, D., Quaglino, D., Bochicchio, B., Pasquali Ronchetti, I., et al. (2006). Figure 1. The flexibility of the mid-region of the molecule was proposed to drive the overall elasticity of the resultant fibers. This acquisition and the development of a next generation of injectables based on this technology will ensure Allergan offers innovative filler products for years to come., Robert Daniels, Elastagen CEO, noted: Partnering with Allergan, a leader in medical aesthetics, is incredibly exciting. The hydrophobic domains vary in length, with the majority of the shorter (95 residues) domains occurring near the N-terminus, while the longer (up to 55 residues) domains are found within tropoelastins central and C-terminal regions (Indik et al., 1989). Natl. 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. 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). FEBS J. (1981). Founder, Elastagen Pty Ltd (sold to Allergan/AbbVie . 3, 4 Elastin has a very low rate of turnover, so it . doi: 10.1074/jbc.M004265200, Kadler, K. E. (2017). Fabricating organized elastin in vascular grafts. Detailed Description: Form. (1988). 2:e1501145. doi: 10.1021/bi9707133, MacEwan, S. R., Weitzhandler, I., Hoffmann, I., Genzer, J., Gradzielski, M., and Chilkoti, A. doi: 10.1016/0005-2795(73)90368-1, Franzblau, C., Faris, B., and Papaioannou, R. (1969). A Study to Evaluate the Efficacy of ELAPR002f in Females and Males With No use, distribution or reproduction is permitted which does not comply with these terms. doi: 10.1016/j.jsb.2004.11.005, Muiznieks, L. D., Jensen, S. A., and Weiss, A. S. (2003). Effect of peptide sequence on the LCST-like transition of elastin-like peptides and elastin-like peptidecollagen-like peptide conjugates: simulations and experiments. doi: 10.1074/jbc.M609505200, Dyksterhuis, L. B., Baldock, C., Lammie, D., Wess, T. J., and Weiss, A. S. (2007). The cross-linking domains are enriched for either Lys-Pro (KP) or Lys-Ala (KA) motifs and form cross-links that link growing tropoelastin chains during elastogenesis; note that exon 6 encodes a KA domain. Free energy determinants of secondary structure formation: I. alpha-Helices. 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). 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 (). Elastic fiber formation: a dynamic view of extracellular matrix assembly using timer reporters. doi: 10.1073/pnas.1812951116, Yue, K., Li, X., Schrobback, K., Sheikhi, A., Annabi, N., Leijten, J., et al. Molecular model of human tropoelastin and implications of associated mutations. 87, 18281834. 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). Cross-linking domains can be subdivided into KP or KA domains, which denote the amino acids (proline or alanine, respectively) that are adjacent to the lysines (Figure 1). Eng. AW gratefully acknowledges NHMRC funding (Ref: 1195827). Most organisms contain one copy of ELN, other than teleosts and amphibians which notably possess two distinct types of ELN genes (He et al., 2007; Miao et al., 2007, 2009). Allergen Acquires Elastagen - pharmasalmanac.com 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. Tropoelastin is a precursor protein of elastin, and is composed of hydrophilic (lysine, valine and proline) and hydrophobic (glycine, valine and proline) domains. J. Biol. J. Computational models have also been leveraged to pinpoint the molecular consequences of synthetic and disease mutations of tropoelastin. Biotechnol. Allergan's Acquisition of Elastagen - Global Legal Chronicle Conformational transitions of the cross-linking domains of elastin during self-assembly. It's a stretchy protein that resembles a rubber band it can stretch out (extend) and shrink back (recoil). II. Collapse Section. Exp. Elastin combines with microfibrils to form elastic fibers that provide stretch and recoil to the skin. Tropoelastin #5052. Novel Recombinant Tropoelastin Implants Restore Skin Extracellular Matrix Biol. Thus, the current computational model unifies the global and regional characteristics of tropoelastin, inferring mechanisms that complement observed experimental phenomena. In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. J. Biol. Cellular activities are mediated through interactions between tropoelastin or EDPs and specific receptors on the cell surface. Pediatr. Recycling of the 67-kDa elastin binding protein in arterial myocytes is imperative for secretion of tropoelastin. Tropoelastin: a novel marker for plaque progression and instability. doi: 10.1016/s0022-5320(83)80021-5, Broekelmann, T. J., Kozel, B. Caterpillar | Caterpillar to Relocate Global Headquarters to Dallas Pharmacol. 250, 9298. Elastin is a critical skin protein consisting of crosslinked tropoelastin. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry. The evolutionary background and functional consequences of the rs2071307 polymorphism in human tropoelastin. A., and Rucker, R. B. Tropoelastin is a spring-like molecule that is extremely extensible prior to cross-linking. Matrix Biol. Unlike other companies that use paid endorsements and questionable data, NULASTIN science is proven by 3rd party clinical evaluation. 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). (2016). doi: 10.1016/j.jsb.2005.02.005, Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995). 37, 698702. Biochem. 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). It has been postulated that the interaction between tropoelastin and cell surface proteoglycans is part of the assembly process of elastin before it is deposited on microfibrils. 284, 22162230. Proline-poor hydrophobic domains modulate the assembly and material properties of polymeric elastin. 150, 154162. Int. 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. Biophys. Initially, in vitro coacervation is characterized by the rapid aggregation of tropoelastin. Further to this, the flexibility of the hydrophobic domains may also play a key role in self-assembly. 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 .