A tunable affinity fusion tag for protein self-assembly
Kimbrough, H.; Jensen, J.; Miller, T.; Lange, J. J.; Halfmann, R.
Show abstract
The concentrations of individual proteins vary between cells, both developmentally and stochastically. The functional consequences of this variation remain largely unexplored due to limited experimental tools to manipulate the relationship of protein concentration to activity. Here, we introduce a genetically encoded tool based on a tunable amyloid that enables precise control of protein concentration thresholds in cells. By systematically screening dipeptide repeats, we identified poly-threonine alanine (poly-TA) as an ideal candidate due to its unique ability to form amyloid-like assemblies with a negligible nucleation barrier at arbitrarily chosen concentration thresholds. We demonstrate that the saturating concentration (Csat) of poly-TA can be finely tuned by adjusting the length of uninterrupted TA repeats, even while maintaining length and composition, providing a modular system for manipulating protein solubility. This tool offers a powerful approach to investigate the relationship between protein concentration, phase separation, and cellular function, with potential applications in cell-, developmental-, and synthetic biology.
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