Optogenetic control of protein binding using light-switchable nanobodies

Agnieszka A. Gil, César Carrasco-López, Liyuan Zhu, Evan M. Zhao, Pavithran T. Ravindran, Maxwell Z. Wilson, Alexander G. Goglia, José L. Avalos, Jared E. Toettcher

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2 Scopus citations

Abstract

A growing number of optogenetic tools have been developed to reversibly control binding between two engineered protein domains. In contrast, relatively few tools confer light-switchable binding to a generic target protein of interest. Such a capability would offer substantial advantages, enabling photoswitchable binding to endogenous target proteins in cells or light-based protein purification in vitro. Here, we report the development of opto-nanobodies (OptoNBs), a versatile class of chimeric photoswitchable proteins whose binding to proteins of interest can be enhanced or inhibited upon blue light illumination. We find that OptoNBs are suitable for a range of applications including reversibly binding to endogenous intracellular targets, modulating signaling pathway activity, and controlling binding to purified protein targets in vitro. This work represents a step towards programmable photoswitchable regulation of a wide variety of target proteins.

Original languageEnglish (US)
Article number4044
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Gil, A. A., Carrasco-López, C., Zhu, L., Zhao, E. M., Ravindran, P. T., Wilson, M. Z., Goglia, A. G., Avalos, J. L., & Toettcher, J. E. (2020). Optogenetic control of protein binding using light-switchable nanobodies. Nature communications, 11(1), [4044]. https://doi.org/10.1038/s41467-020-17836-8