Elastin assembly

S.M. Mithieux, S.G. Wise, M.J. Raftery, B. Starcher, A.S. Weiss, A model two-component system for studying the architecture of elastin assembly in vitro, J. Struct. Biol. 149 (2005) 282—289. 

Wright E.R., McMillan R., Andrew C.A., Apkarian, R.P., and Conticello, V.P. Thermoplastic elastomer hydrogels via self-assembly of an elastin-mimetic triblock polypeptide, Adv. Func. Mater., 12, 149, 2002. 

Lee T.A.T., Cooper A., Apkarian R.P., and Conticello V.P. Thermo-reversible self-assembly of nano-particles derived from elastin-mimetic polypeptides. Advanced Materials, 12, 1105, 2000. 

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

Miao, M., Cimlis, J.T., Lee, S., and Keeley, F.W., Stmctural determinants of cross-hnking and hydro-phobic domains for self-assembly of elastin-hke pol3fpeptides. Biochemistry, 44(43), 14367-14375, 2005. 

Keeley, F.W., Bellingham, C.M., and Woodhouse, K.A., Elastin as a self-organising biomaterial Use of recombinantly expressed human elastin polypeptides as a model system for investigations of structure and self-assembly of elastin, Philos. Trans. R. Soc. Lond. B Biol. Sci., 357, 185-189, 2002. 

Belhngham, C.M., Lillie, M.A., Gosline, J.M., Wright, G.M., Starcher, B.C., Bailey, A.J., Woodhouse, K.A., and Keeley, F.W., Recombinant human elastin polypeptides self-assemble into biomaterials with elastin-hke... 

The first elastomeric protein is elastin, this structural protein is one of the main components of the extracellular matrix, which provides stmctural integrity to the tissues and organs of the body. This highly crosslinked and therefore insoluble protein is the essential element of elastic fibers, which induce elasticity to tissue of lung, skin, and arteries. In these fibers, elastin forms the internal core, which is interspersed with microfibrils [1,2]. Not only this biopolymer but also its precursor material, tropoelastin, have inspired materials scientists for many years. The most interesting characteristic of the precursor is its ability to self-assemble under physiological conditions, thereby demonstrating a lower critical solution temperature (LCST) behavior. This specific property has led to the development of a new class of synthetic polypeptides that mimic elastin in its composition and are therefore also known as elastin-like polypeptides (ELPs). 

This coacervation process forms the basis for the self-assembly, which takes place prior to the crosslinking. The assembly of tropoelastin is based on an ordering process, in which the polypeptides are converted from a state with little order to a more structured conformation [8]. The insoluble elastic fiber is formed via the enzymatic crosslinking of tropoelastin (described in Sect. 2.1). Various models have been proposed to explain the mechanism of elasticity of the elastin fibers. 

Miao M, Cirulis JT, Lee S et al (2005) Structural determinants of cross- linking and hydrophobic domains for self-assembly of elastin-like polypeptides. Biochemistry 44 14367-14375... 

The pattern of inheritance of Marfan syndrome is autosomal dominant due to the failure of elastic fibers to assemble properly upon interaction of mutant fibrillin with normal elastin. 

Fibrillin microfibrils are widely distributed extracellular matrix assemblies that endow elastic and non elastic connective tissues with long-range elasticity. They direct tropoelastin deposition during elastic fibrillogenesis and form an outer mantle for mature elastic fibers. Microfibril arrays are also abundant in dynamic tissues that do not express elastin, such as the ciliary zonules of the eye. Mutations in fibrillin-1—the principal structural component of microfibrils—cause Marfan syndrome, a heritable disease with severe aortic, ocular, and skeletal defects. Isolated fibrillin-rich microfibrils have a complex 56 nm beads-on-a-string appearance the molecular basis of their assembly and... 

In developing elastic tissue, the microfibrils are the first components to appear in the extracellular matrix. They are then thought to act as a scaffold for deposition, orientation, and assembly of tropoelastin monomers. They are 10—12 nm in diameter, and lie adjacent to cells producing elastin and parallel to the long axis of the developing elastin fiber (Cleary, 1987). 

Brown-Augsburger, P., Tisdale, C., Broekelmann, T., Sloan, C., and Mecham, R. P. (1995). Identification of an elastin cross-linking domain that joins three peptide chains. Possible role in nucleated assembly./. Biol. Chem. 270, 17778-17783. 

Mithieux, S. M., Rasko, J. E., and Weiss, A. S. (2004). Synthetic elastin hydrogels derived from massive elastic assemblies of self-organized human protein monomers. Biomaterials 25, 4921-4927. 

In Nature, there are many examples of protein and peptide molecular self-assembly. Of the genetically engineered fibrous proteins, collagen, spider silks, and elastin have received attention due to their mechanical and biological properties which can be used for biomaterials and tissue engineering. 

This review focuses upon the post-translational modification and chemical changes that occur in elastin. Outlined are the steps currently recognized as important in the assembly of pro-fibrillar elastin subunits into mature fibers. Descriptions of some of the proposed mechanisms that appear important to the process are also presented. It will be emphasized that from the standpoint of protein deterioration, elastin is a very novel protein. Under normal circumstances, the final product of elastin metabolism, the elastin fiber does not undergo degradation that is easily measured. Unlike the metabolism of many other proteins, deterioration or degradation is most evident biochemically in the initial stages of synthesis rather than as a consequence of maturation. Since the presence of crosslinks is an essential component of mature elastin, a section of this review also addresses important features of crosslink formation. 

Figure 2. Synthesis of mature elastin fibers. Some evidence suggests the possibility for proforms to elastin that appear as the first products of translation. These products are cleaved to tropoelastin (27), which appears to combine with microfibrillar protein. Although post-translational events important to the synthesis of the microfibrillar protein have not been defined, it is clear that it is a major component on which is organized or assembled the profibrillar forms of elastin. Cross-linking is catalyzed by lysyl oxidase, a copper-requiring protein (30). Recent information on the elastin proteinase(s) involved in tropoelastolysis would suggest that proteolysis may also play a role in elastin fiber...

A triple helix forming collagen model peptide and a thermosensitive elastin derived pentapeptide are copolymerized using EDCCl and HOBt in DMSO. A comparison of BrCN and EDC in assembling modified DNA duplexes and DNA-RNA hybrids shows that higher yields are obtained with the slower reacting EDC. ... 

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