Bacterial Phytochrome as a Scaffold for Engineering of Receptor Tyrosine Kinases Controlled with Near-Infrared Light

Anna V. Leopold, Sergei Pletnev, Vladislav V. Verkhusha

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Optically controlled receptor tyrosine kinases (opto-RTKs) allow regulation of RTK signaling using light. Until recently, the majority of opto-RTKs were activated with blue-green light. Fusing a photosensory core module of Deinococcus radiodurans bacterial phytochrome (DrBphP-PCM) to the kinase domains of neurotrophin receptors resulted in opto-RTKs controlled with light above 650 nm. To expand this engineering approach to RTKs of other families, here we combined the DrBpP-PCM with the cytoplasmic domains of EGFR and FGFR1. The resultant Dr-EGFR and Dr-FGFR1 opto-RTKs are rapidly activated with near-infrared and inactivated with far-red light. The opto-RTKs efficiently trigger ERK1/2, PI3K/Akt, and PLCγ signaling. Absence of spectral crosstalk between the opto-RTKs and green fluorescent protein-based biosensors enables simultaneous Dr-FGFR1 activation and detection of calcium transients. Action mechanism of the DrBphP-PCM-based opto-RTKs is considered using the available RTK structures. DrBphP-PCM represents a versatile scaffold for engineering of opto-RTKs that are reversibly regulated with far-red and near-infrared light.

Original languageEnglish (US)
Pages (from-to)3749-3760
Number of pages12
JournalJournal of Molecular Biology
Volume432
Issue number13
DOIs
StatePublished - Jun 12 2020

Keywords

  • DrBphP
  • EGFR
  • FGFR1
  • bacteriophytochrome
  • opto-RTK

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology

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