Toward a molecular mechanism for the interaction of ATP with alpha-synuclein.

ABSTRACT: The ability of Adenosine Triphosphate (ATP) to modulate protein solubility establishes a critical link between ATP homeostasis and proteinopathies, such as Parkinson's (PD). The most significant risk factor for PD is aging, and ATP levels decline dramatically with age. However, the mechanism by which ATP interacts with alpha-synuclein (αS), whose aggregation is characteristic of PD, is currently not fully understood, as is ATP's effect on αS aggregation. Here, we use nuclear magnetic resonance spectroscopy as well as fluorescence, dynamic light scattering and microscopy to show that ATP affects multiple species in the αS self-association cascade. The triphosphate moiety of ATP disrupts long-range electrostatic intramolecular contacts in αS monomers to enhance initial aggregation, while als

SUBMITTER: Kamski-Hennekam ER 

PROVIDER: S-EPMC10510630 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature