Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

摘要: As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation intermediates, but identifying these within the dynamic ensemble of is difficult. Herein, we used biologically relevant calcium ion investigate conformation aSyn in relation its propensity. We observe that more exposed N-terminus beginning NAC region are, become. Solvent exposure occurs upon release C-terminus interactions when binds, level aSyn's propensity sequence post translational modification dependent. Identifying environmental conditions they form under will allow us design new therapeutics targeted protein.