Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells.
Brophy, Jennifer AN
Springer Science and Business Media LLC
MetadataShow full item record
Cuevas-Velazquez, C. L., Vellosillo, T., Guadalupe, K., Schmidt, H. B., Yu, F., Moses, D., Brophy, J. A., et al. (2021). Intrinsically disordered protein biosensor tracks the physical-chemical effects of osmotic stress on cells.. Nat Commun, 12 (1), 5438. https://doi.org/10.1038/s41467-021-25736-8
Cell homeostasis is perturbed when dramatic shifts in the external environment cause the physical-chemical properties inside the cell to change. Experimental approaches for dynamically monitoring these intracellular effects are currently lacking. Here, we leverage the environmental sensitivity and structural plasticity of intrinsically disordered protein regions (IDRs) to develop a FRET biosensor capable of monitoring rapid intracellular changes caused by osmotic stress. The biosensor, named SED1, utilizes the Arabidopsis intrinsically disordered AtLEA4-5 protein expressed in plants under water deficit. Computational modeling and in vitro studies reveal that SED1 is highly sensitive to macromolecular crowding. SED1 exhibits large and near-linear osmolarity-dependent changes in FRET inside living bacteria, yeast, plant, and human cells, demonstrating the broad utility of this tool for studying water-associated stress. This study demonstrates the remarkable ability of IDRs to sense the cellular environment across the tree of life and provides a blueprint for their use as environmentally-responsive molecular tools.
Cell Line, Tumor, Osteoblasts, Humans, Escherichia coli, Saccharomyces cerevisiae, Arabidopsis, Water, Molecular Chaperones, Arabidopsis Proteins, Recombinant Proteins, Fluorescence Resonance Energy Transfer, Biosensing Techniques, Gene Expression, Binding Sites, Protein Conformation, Protein Binding, Kinetics, Osmolar Concentration, Osmotic Pressure, Thermodynamics, Models, Molecular, Protein Interaction Domains and Motifs, Intrinsically Disordered Proteins
External DOI: https://doi.org/10.1038/s41467-021-25736-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330942
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/