Kinetic investigation of calcium-induced Sorcin aggregation by stopped-flow light scattering

Sorcin, a penta-EF hand calcium-binding protein, is implicated in multidrug resistance (MDR) in various cancers and has roles in neurodegenerative diseases. It regulates cellular calcium homeostasis by interacting with calcium channels, pumps, and exchangers in a calcium-dependent manner. Calcium binding induces a conformational change in Sorcin, exposing hydrophobic surfaces that mediate protein interactions and calcium flux between the cytosol and endoplasmic reticulum. These exposed surfaces can also drive Sorcin aggregation in the absence of binding partners. Here, we exploited calcium-induced conformational changes and aggregation of Sorcin as a model to study its calcium sensitivity and aggregation mechanisms. Stopped-flow light scattering revealed that Sorcin aggregation is reversible, co-operative, and primarily influenced by Sorcin concentration rather than physiological calcium levels. Our findings suggest that the calcium sensitivity of Sorcin is finely tuned by its expression level, highlighting its role as an intracellular calcium sensor. This work establishes Sorcin as a model system for studying protein aggregation mechanisms with implications for MDR and neurodegenerative diseases.