Elastin structure models

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. 

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. 

In almost all instances of biological mineralization fibrous proteins represent the bulk of the organic matrix. In the past, this phenomenon has been interpreted to mean that proteins such as collagen, keratin or elastin are the key elements in mineralization by providing nucleation sites and at the same time offering structure and space for oriented crystal growth. However, with the advance in the field of biomineralization this model came under severe attack. At present, there is no universal concept which could explain all the intriguing facets of phosphate deposition in cellular systems. 

Numerous studies have been undertaken to elucidate the secondary structure of soluble elastin. These studies have been performed on elastin, elastin solubilized by oxalic acid (a-elastin) or potassium hydroxide (/, -elastin). synthetic polypeptide models of elastin, and tropoelastin. Techniques used include circular dichroism, FT-Raman, and electron microscopy. No consensus has been reached on the overall structure of elastin. 

The fundamental driving force behind the remarkable elastic properties of the elastin polymer is believed to be entropic, where stretching decreases the entropy of the system and elastic recoil is driven by a spontaneous return to maximum entropy. The precise molecular basis for elasticity has not been fully elucidated and a number of models exist. Two main categories of structure-function models have been proposed those in which elastin is considered to be isotropic and devoid of structure, and those which consider elastin to be anisotropic with regions of order (Vrhovski and Weiss, 1998). 

Abstract The utility of confocal Raman microscopy to study biological events in skin is demonstrated with three examples, (i) monitoring the spatial and structural differences between native and cultured skin, (ii) tracking the permeation and biochemical transformation in skin of a Vitamin E derivative and (iii) tracking the spatial distribution of three major skin proteins (keratin, collagen, and elastin) during wound healing in an explant skin model. 

Elastin is a macromolecule synthesized as a 70,000 single peptide chain, termed tropoelastin and secreted into the extracellular matrix where it is rapidly crosslinked to form mature elastin. The carboxy-terminal end of elastin is highly conserved with the sequence Gly-Gly-Ala-Cys-Leu-Gly-Leu-Ala-Cys-Gly-Arg-Lys-Arg-Lys. The two Cys residues that form disulfide crosslinks are found in this region as well as a positively charged pocket of residues that is believed to be the site of interaction with microfibrillar protein residues. Hydrophobic alanine-rich sequences are known to form a helices in elastin these sequences are found near lysine residues that form crosslinks between two or more chains. Alanine residues not adjacent to lysine residues found near proline and other bulky hydrophobic amino acids inhibit a helix formation. Additional evidence exists for (3 structures and 3 turns within elastin thereby giving an overall model of the molecule that contains helical stiff segments connected by flexible segments. 

Kasarda, D.D., King, G., and Kumonsinski, T.F. (1994). Comparison of p-spiral structures in wheat high molecular weight glutenin subunits and elastin by molecular modelling. In ... 

Further changes in the P1-P5 region, which resulted in improved efficacy for these synthetic substrates, were based on elastin, HLE s natural substrate [36]. This excellent substrate is an insoluble, structural protein, which is primarily composed of hydrophobic amino acid residues. However, it also contains a number of Lys-derived, cross-linked residues, such as desmosine and isodesmosine, that incorporate a positively charged pyridinium ring. In order to model this cross-linking feature, Lys or various amino-protected forms of Lys, were systematically incorporated into the substrate MeO-8uc-Ala-Ala-Pro-Val-NA (4-1). Replacement of any single residue with Lys led to decreased activity, for example, (4-2)-(4-4) Table 2.4). However, the use of side-chain protected Lys derivatives (e.g. the NHj terminus protected with benzyloxycarbonyl or picolinyl) led to increased reactivity to elastase with the optimal position for substitution being P4, see (4-5)-(4-8). 

Several models of the macromolecular structure of elastin have been suggested to account for its elasticity cross-linked globular elastin subunits, cross-linked... 

In one study, a model for elastin, the main protein that confers elasticity on solid structures in mammals, had its mobility investigated by examining 1H-13C and 1H dipolar couplings extracted from isotropic-anisotropic correlation experiments.29 The elastic properties of elastin are almost certainly conferred by molecular degrees of freedom, so such studies are important in understanding how this material works in Nature. The motional amplitudes determined from these experiments were found to depend upon the degree of hydration, with the mean square fluctuation angles found to be 11-18° in the dry protein and 16-21° in the 20% hydrated protein. 

Seminal work by Urry on cyclic analogs of elastin revealed a Pro-Gly type II P-tum by NMR and crystallography, which served as the basis for the P-spiral model (22,23,24). The model described a structure in which consecutive p-tums formed a helical arrangement. In this structure, there was one type II P-tum per pentameric unit of elastin, which served as spacers between the spiral turns. Further evidence for this p-spiral stmcture was compiled by molecular dynamic... 

Silk. Structural studies of the model peptides of Bombyx mori silk-elastin like protein were undertaken using solid state NMR. Detailed structural analyses were performed using deconvolution subroutines assuming Gaussian line shapes for the Ala peaks. 

D.W. Urry,T. Hugel, M. Seitz, H. Gaub, L. Sheiba, J. Dea, J. Xu, L. Hayes, F. Prochazka, and T. Parker, Ideal Protein Elasticity The Elastin Model. In Elastomeric Proteins Structures, Biomechanical Properties and Biological Roles P.R. Shewry, A.S. Tatham, and A.J. Bailey, Eds. Cambridge University Press, The Royal Society Chapter Four, pages 54-93,2003. 

Early in our studies it was expected that the post-translational modification of proline hydroxylation, so important to proper collagen structure and function, would raise the value of the temperature, T, for the onset of the inverse temperature transition for models of elastin. Accordingly, hydroxyproline (Hyp) was incorporated by chemical synthesis into the basic repeating sequence to give the protein-based polymers poly[fvs,i(Val-Pro-Gly-Val-Gly), fHyp( al-Hyp-Gly-Val-Gly)], where f sl -i- fnyp = 1 and values of fnyp were 0, 0.01, and 0.1. The effect of prolyl hydroxylation is shown in Figure 7.49. Replacement of proline by hydroxyproline markedly raises the temperature for hydrophobic association. Prolyl hydroxylation moves the movable cusp of... 

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