Conversion of human α-synuclein (aS) from the free soluble state to the insoluble fibrillar state has been implicated in the etiology of Parkinson’s disease. Human aS is highly homologous in amino acid sequence to mouse aS which contains seven substitutions including the A53T substitution that is the same as the one that has been linked to familial Parkinson’s disease, and including five substitutions in the C terminal region. It has been shown that the rate of fibrillation is highly dependent on the exact sequence of the protein and mouse aS is reported to aggregate more rapidly than human aS in vitro. Nuclear magnetic resonance of mouse aS and human aS at supercooled temperatures (263K) is used to understand the effect of sequence on conformational fluctuations in the disordered ensembles and to relate these to differences in propensities to aggregate. We show that human and mouse aS are natively unfolded at low temperature but that they exhibit different propensities to secondary structure, backbone dynamics and long range contacts across the protein. Mouse aS exhibits a higher propensity to helical conformation at the C terminal substitution sites as well as the loss of transient long range contacts from the C terminal end to the N terminal and hydrophobic central region of the protein relative to human aS. Lack of back-folding from the C terminal end of mouse aS exposes the N terminal region which is shown, by 15N relaxation experiments, to be very restricted in mobility relative to human aS. We propose that the restricted mobility in the N terminal region may arise from transient interchain interactions suggesting that the N-terminal KTK(E/Q)GV hexamer repeats may serve as initiation sites for aggregation in mouse aS. These transient interchain interactions of the N terminal region coupled with a non-Aβ amyloid component (NAC) region that is both more exposed and has a higher propensity to β structure may explain the increased rate of fibril formation of mouse aS relative to human aS and A53T aS.