📝 SummarXiv

Abstract

We employ a multiscale computational approach to investigate the condensation process of the C-terminal low-complexity region of the Caprin1 protein as a function of increasing ATP concentration for three states: the initial mixed state, nanocondensate formation, and the dissolution of the droplet as it reenters the mixed state. We show that upon condensation ATP assembles via pi-pi interactions, resulting in the formation of a large cluster of stacked ATP molecules stabilized by sodium counterions. The surface of the ATP assembly interacts with the arginine-rich regions of the Caprin1 protein, particularly with its N-terminus, to promote the complete phase-separated droplet on a lengthscale of tens of nanometers. In order to understand droplet stability, we analyze the near-surface electrostatic potential (NS-ESP) of Caprin1 and estimate the zeta potential of the Caprin1-ATP assemblies. We predict a positive NS-ESP at the Caprin1 surface for low ATP concentrations that defines the early mixed state, in excellent agreement with the NS-ESP obtained from NMR experiments using paramagnetic resonance enhancement. By contrast, the NS-ESP of Caprin1 at the surface of the nanocondensate at moderate levels of ATP is highly negative compared to the mixed state, and estimates of a large zeta potential outside the highly dense region of charge further explains the remarkable stability of this phase separated droplet assembly. As ATP concentrations rise further, the strong electrostatic forces needed for nanocondensate stability are replaced by weaker Caprin1-ATP interactions that drive the reentry into the mixed state that exhibits a much lower zeta potential.