alpha-Synuclein enhances bioluminescent activity of firefly luciferase by facilitating luciferin localization

alpha-Synuclein, the pathological component of Parkinson's disease, has been demonstrated to be highly interactive with various protein partners. alpha-Synuclein has been shown to exert a novel effect on the bioluminescence of firefly luciferase by stimulating the oxyluciferin formation from its substrate of luciferin, which results in a significant enhancement of the spike of flashing light via concomitant augmentation for both rapid rise and quick decay of the luminescence. Binding affinity between alpha-synuclein and luciferase was evaluated with K(d) of 8.1 microM based on a dose-dependent enhancement of the luciferase activity by alpha-synuclein. Kinetic analyses indicated that alpha-synuclein has facilitated luciferin localization to the luciferase by decreasing apparent K(m), which makes the maximum rate of bioluminescence no longer dependent upon ATP concentration. Catalytic consequences of the alpha-synuclein binding to luciferase have led to a delayed onset of the coenzyme A-mediated retardation of the quick decay of flashing light as well as a shift in the emission spectra of bioluminescence. Taken together, the novel effects of alpha-synuclein toward the bioluminescence of luciferase have been demonstrated to be initiated by the specific molecular interaction between the proteins which has influenced the substrate (luciferin) localization to the enzyme.