ZOOMING ON THE INTERACTION BETWEEN a-SYNUCLEIN AND CALCIUM IONS APPROACHING PHYSIOLOGICAL CONDITIONS

Intrinsically disordered proteins (IDPs) and protein regions (IDRs) lack a stable 3D structure but are nevertheless functional thanks to their dynamic properties. Their fine-tuned features are expected to be modulated by side- chains as well as local solvent exposure so it is crucial to characterize them with atomic-resolution approaches. Here we propose a 13C based strategy to provide a unique tool to investigate IDPs behavior in different experimental conditions relevant for their physiological function. A set of carbonyl carbon direct detected NMR experiments was implemented to monitor the IDPs/IDRs both from the backbone and side chains point of view. The latter is seldom studied in highly flexible and disordered proteins because of extensive signal overlap . In addition, a novel pulse sequence based on the CON experiment was designed to achieve information of amide proton exchange with the solvent (DeCON). This set of experiments was used to obtain a fingerprint of a-synuclein that is fully disordered in its native conditions and to study the interplay between this IDP and Ca2+ ions , zooming into the metal ion coor- dination sphere and revealing the motifs involved in the interaction