Structural changes and facilitated association of tropoelastin

Circular dichroism studies of tropoelastin secondary structure show 4±1% α-helix in aqueous solutions. This is in contrast to the substantially higher amounts (up to 23±7%) of α-helix predicted by computer algorithms, which propose that regions of α-helix are limited to the alanine-rich cross-linking domains. Through the addition of trifluoroethanol, the amount of α-helix increased to 17±1%, equivalent to that expected on the basis of primary structure. The physiological ability of the protein to coacervate and the critical concentration of monomer required for coacervation were unaffected by levels of α-helix. However, the temperature required for coacervation decreased linearly with increasing α-helical structure, which correlates with the participation of α-helices in association. We propose that the alanine-rich cross-linking domains exist as nascent helices in tropoelastin in aqueous solution. We further suggest a novel mechanism for coacervation whereby formation of α-helices and subsequent helical side chain interactions limit the conformational flexibility of the polypeptide, to facilitate associations between hydrophobic domains during elastogenesis.