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THz spectroscopy study of amyloid fibrils

  • Autori: Piccirilli, F; Schirò, G; Vetri, V; Cupane, A; Leone, M; Militello, V
  • Anno di pubblicazione: 2013
  • Tipologia: Altro
  • OA Link:


In suitable conditions proteins can modify their native conformation and associate to form aggregates with different morphologies in dependence on the external physico-chemical conditions. This phenomenon, one of the most challenging in life sciences, is associated with widely diffused pathologies such as Alzheimer’s, Parkinson’s and Creutzfeldt-Jacob’s diseases. Of particular relevance are ordered elongated aggregates with highly organized patterns of hydrogen-bonds, known as amyloid fibrils. While much biological and structural information are available about amyloids, and in spite of the fundamental paradigm of structure-dynamics-function relation in proteins, much less is known about their dynamics. In the last decade the application of THz spectroscopy to biological samples is subject of renewed interest since it promises to give important information on protein dynamics by probing delocalised vibrational modes that depend on the overall structure. Moreover, THz absorption spectroscopy provides a sensitive tool for probing the fast hydration water dynamics (ps range) around. Based on the importance of the relationship between protein dynamics in the ps range, which involves side-chains and backbone fluctuations, and protein function and in the light of the functional relevance of amyloidal aggregation, it is of utmost importance to study the dynamical behaviour of proteins in their aggregated state. Recently, neutron scattering measurements, which probe protein dynamics in the same time scale of THz spectroscopy, have shown enhanced atomic fluctuations in Concanavalin A (ConA) amyloid fibrils, at temperatures above the dynamical transition (>230 K), where protein motions are coupled to hydration water dynamics. This behaviour was explained inferring that the structural constraints leading to amyloid formation bring proteins to expose side-chains to the fibril surface, thus lowering the steric hindrance from other amino acids and allowing the “plasticizing” interaction with hydration water. The importance of studying ConA aggregated states is of interest for a range of scientific applications: ConA agglutinates several eukaryotic cell-types, and shows characteristic binding specificity for bacterial surface-exposed carbohydrates. Also, ConA has significant structural homology to the human serum amyloid protein (SAP) that is present in in vivo amyloid deposits. Finally, the aggregation process of ConA is also associated with its antitumor activity and was found to be related to its property of inducing apoptosis on tumoral cells. We present here the THz absorption study of Concanavalin A (ConA) amyloid fibrils in comparison with the native and the amorphous aggregated state of the same protein. Significant information on the coupling between protein motions and hydration water in the different aggregated species are shown, remarking the dependence on the structural features of the samples of the spanning network of H-bonds between water molecules in the hydration shell. The information obtained from low frequencies modes are coupled and compared to the structural characterization of the aggregates probed by mid infrared absorption and Raman scattering spectroscopies. While unequivocal information about secondary structural moieties can be obtained by the analysis of the proteins mid infrared absorption profile, tertiary folding and lateral chains spatial arrangment can be evaluated from the observation of Raman scattering spectrum.