Molecular basis of polyglutamine-modulated ELF3 aggregation in Arabidopsis temperature response

Some plants, like Arabidopsis thaliana, possess a molecular mechanism that allows them to sense changes in temperature and respond by modifying growth rate, photoperiod length and timing of flowering. Underlying this mechanism is a tripartite protein complex called the Evening Complex (EC) that functions as a DNA transcription repressor targeting growth-related genes. ELF3, a large disordered scaffolding protein, is the primary component of the EC. At low temperature ELF3 sits over DNA targets occluding transcription machinery and halting growth. Rising temperature promote ELF3 condensate formation as it becomes sequestered in large reversible nuclear condensates allowing DNA transcription and plant growth to proceed. A C-terminal prion-like domain (PrD) has been observed to be sufficient for ELF3 aggregation. Within this PrD region lies a poly-glutamine repeat of variable length, the size of which has been found to modulate the thermal responsiveness as measured by hypocotyl (stem) elongation and condensate formation. We use a polymer chain growth approach to build large ensembles and characterize monomeric ELF3-PrD at a range of polyQ lengths and temperatures. We then explore temperature-dependent dynamics of wild-type ELF3-PrD and a mutant, F527A, using chain growth structures as initial conformations for replica exchange (REST2) simulations. We find increased solvent accessibility of expanded polyQ tracts, promotion of temperature-sensitive helices adjacent to polyQ tracts, and exposure of a cluster of aromatic residues at increased temperature, all three of which promote inter-protein interaction. Protein condensate formation is a ubiquitous but poorly understood mechanism implicated in a range of biological functions and malfunction. Our computational approach to understanding the molecular basis for the temperature sensitivity of this system has wider implications on the understanding of phenomena regulating condensate formation more generally.