Metal ions shape α-synuclein.

摘要: α-Synuclein is an intrinsically disordered protein that can self-aggregate and plays a major role in Parkinson's disease (PD). Elevated levels of certain metal ions are found aggregates neurons people suffering from PD, environmental exposure has also been linked with neurodegeneration. Importantly, cellular interactions ions, particularly Ca2+, have recently reported as key for α-synuclein's physiological function at the pre-synapse. Here we study effects ion interaction α-synuclein molecular level, observing changes conformational behaviour monomers, possible link to aggregation pathways toxicity. Using native nano-electrospray ionisation mobility-mass spectrometry (nESI-IM-MS), characterize heterogeneous alkali, alkaline earth, transition other their global structural on α-synuclein. Different binding stoichiometries upon titration correlate specific affinity capacity. Subtle seen singly charged metals differ profoundly multiply often leading overall compaction depending preferred sites. This illustrates coordination, associated electrostatic charge patterns, complex space