Unraveling the Hydration Dynamics of the ACC1-13K24-ATP System: From Liquid-to-Droplet to-Amyloid Fibril.

Abstract

In order to achieve a comprehensive understanding of protein aggregation processes, an exploration of solvation dynamics, a key yet intricate component of biological phenomena, is mandatory. In the present study, we used Fourier Transform Infrared Spectroscopy (FT-IR) and Terahertz(THz)-spectroscopy complemented by Atomic Force Microscopy and kinetic experiments utilizing Thioflavin T (ThT) fluorescence to elucidate the changes in solvation dynamics during liquid-liquid phase separation and subsequent amyloid fibril formation, the latter representing a transition from liquid to solid phase separation. These processes are pivotal in the pathology of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. We focus on the ACC1-13K24-ATP protein complex, which undergoes fibril formation followed by droplet generation. Our investigation reveals the importance of hydration as a driving force in these processes, offering new insights into the molecular mechanisms at play.