Systems Biology lab group meeting will take place on
Monday, November 1/8, 2021
10:00am ET
Virtual
Presenter:
Justin Lindsay, Ph.D.,
Structural & Molecular Biophysics Collaboration, Center for Computational Biology
Poly-glutamine tract length modulates temperature sensitivity in Arabidopsis by altering liquid-liquid phase separation dynamics of ELF3
Many plants, such as Arabidopsis thaliana, have adapted to sense increasing temperature and respond by up-regulating genes responsible for growth. Recent studies have identified a three-protein circadian clock component, the Evening Complex (EC), a transcription repressor thought to be responsible for integrating temporal information with thermal signals from the environment to quickly enable this genetic response. One of these proteins, ELF3, contains a C-terminal prion-like domain (PrD) responsible for aggregation of the protein into large condensates, removing the complex from DNA and freeing up growth-related genes for transcription. Within this PrD region lies a poly-glutamine repeat of variable length, the size of which has been found to modulate the degree of thermal responsiveness as measured by hypocotyl elongation. Here, we investigate the impact of polyQ tract length on the structure of ELF3-PrDs at a range of temperatures. We characterize ELF3-PrD at the monomer level by utilizing a hierarchical chain-growth method to build atomic resolution ensembles at each condition, and seek to understand the factors that differentiate the phase behavior observed as polyQ length varies. Beyond temperature responsiveness in plants, PolyQ-modulated liquid-liquid phase separation is implicated in an ever-increasing number of biological processes, like stress responses and chromatin organization, and diseases, most prominently Huntington’s disease and ALS, underscoring the value a clearer understanding of this mechanism could bring.
Monday, November 1/8, 2021
10:00am ET
Virtual
Presenter:
Justin Lindsay, Ph.D.,
Structural & Molecular Biophysics Collaboration, Center for Computational Biology
Poly-glutamine tract length modulates temperature sensitivity in Arabidopsis by altering liquid-liquid phase separation dynamics of ELF3
Many plants, such as Arabidopsis thaliana, have adapted to sense increasing temperature and respond by up-regulating genes responsible for growth. Recent studies have identified a three-protein circadian clock component, the Evening Complex (EC), a transcription repressor thought to be responsible for integrating temporal information with thermal signals from the environment to quickly enable this genetic response. One of these proteins, ELF3, contains a C-terminal prion-like domain (PrD) responsible for aggregation of the protein into large condensates, removing the complex from DNA and freeing up growth-related genes for transcription. Within this PrD region lies a poly-glutamine repeat of variable length, the size of which has been found to modulate the degree of thermal responsiveness as measured by hypocotyl elongation. Here, we investigate the impact of polyQ tract length on the structure of ELF3-PrDs at a range of temperatures. We characterize ELF3-PrD at the monomer level by utilizing a hierarchical chain-growth method to build atomic resolution ensembles at each condition, and seek to understand the factors that differentiate the phase behavior observed as polyQ length varies. Beyond temperature responsiveness in plants, PolyQ-modulated liquid-liquid phase separation is implicated in an ever-increasing number of biological processes, like stress responses and chromatin organization, and diseases, most prominently Huntington’s disease and ALS, underscoring the value a clearer understanding of this mechanism could bring.
