Role of polyproline II conformation in human tropoelastin structure

In this review, we present a comprehensive overview of the molecular studies on human tropoelastin domains accomplished by Tamburro and co-workers in the last decade. The used approach is the reductionist approach applied to human tropoelastin and is based on the observation that the tropoelastin gene exhibits a cassette-like organization, with a regular alternation of cross-linking and hydrophobic domains putatively responsible for the elasticity of the protein. The peculiar structure of human tropoelastin gene prompted us to study the isolated domains encoded by the exons of tropoelastin, with the perspective to get deep insights into the structural properties of the whole protein. At the molecular level, the results clearly evidence large flexibility of the polypeptide chains in the hydrophobic domains, which oscillate between rather extended and folded conformations. An important role was assigned to poly-proline II conformation considered as the hinge structure in the dynamic conformational equilibrium suggested for the hydrophobic domains. For the lysine-rich cross-linking domains, the structural studies exactly localized α-helix along the polypeptide sequence. Furthermore, at supramolecular level, these studies showed that several domains are able to self-assemble in two different aggregation patterns, the fibrous elastin-like structure for some proline-rich hydrophobic domains and the amyloid-like for some glycine-rich hydrophobic domains. Accordingly, the studies suggest that the reductionist approach was a valid tool for studying a complex protein, such as elastin, elucidating not only the structure but also the specific role played by its constituent domains.