Optogenetic control of protein binding using light-switchable nanobodies.

TitleOptogenetic control of protein binding using light-switchable nanobodies.
Publication TypeJournal Article
Year of Publication2020
AuthorsGil, AA, Carrasco-López, C, Zhu, L, Zhao, EM, Ravindran, PT, Wilson, MZ, Goglia, AG, Avalos, JL, Toettcher, JE
JournalNat Commun
Date Published2020 08 13
KeywordsAnimals, HEK293 Cells, Humans, Mice, NIH 3T3 Cells, Optogenetics, Protein Binding, Protein Transport, Signal Transduction, Synthetic Biology

<p>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.</p>

Alternate JournalNat Commun
PubMed ID32792536
PubMed Central IDPMC7426870
Grant ListDP2 EB024247 / EB / NIBIB NIH HHS / United States
F30 CA206408 / CA / NCI NIH HHS / United States
F32 GM128304 / GM / NIGMS NIH HHS / United States