Identification of a biological excimer involving protein-protein interactions: A case study of the α-synuclein...

Excimer formation based on pyrene derivatives stacking has been used to probe conformational changes associated with a variety of protein interactions. Herein, in search for the nature of the protein interactions involved in amyloid proteins aggregation we studied the spectroscopic features of the N_α-acetyl-l-tyrosinamide (NAYA) parent compound and of a well-known aggregate amyloid protein, the α-synuclein (Syn). The aggregation of this amyloid disordered protein has been implicated in the development of Parkinson's disease, which is an increasingly prevalent and currently incurable neurodegenerative disorder. Also, Syn aggregation has been widely investigated but, information concerning the conformational alterations in the diverse protein aggregated species at the molecular level, is still scarce. Three different molecular configurations of the NAYA parent compound were at least found to exist in its solutions containing 1,4-dioxane. Two of these NAYA molecular configurations were found to produce a more efficient excimer fluorescence. For Syn solutions containing 1,4-dioxane, one molecular configuration involving the intermolecular interaction between the protein tyrosyl group and the protein peptide bond was found to exhibit excimer fluorescence. This study is the first one reporting the formation of a biological excimer exhibiting fluorescence. Although very weak, this can be used as a signature of protein-protein interactions and, ultimately, enabling to access the complex interactions network existing in the amyloid aggregated species.