Bacterial phytochrome as a scaffold for engineering of receptor tyrosine kinases controlled with near-infrared light
| Autor: | Anna V. Leopold, Vladislav V. Verkhusha, Sergei Pletnev |
|---|---|
| Přispěvatelé: | Department of Anatomy, Faculty of Medicine, Medicum, University of Helsinki |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Light
Protein Conformation Biosensing Techniques Receptor tyrosine kinase Green fluorescent protein ACTIVATION Phosphatidylinositol 3-Kinases 0302 clinical medicine bacteriophytochrome DOMAIN Structural Biology Receptor 0303 health sciences biology Phytochrome Tissue Scaffolds Chemistry Kinase Cell biology FLUORESCENT PROTEINS Crosstalk (biology) embryonic structures Deinococcus Signal Transduction animal structures MAP Kinase Signaling System EGFR Green Fluorescent Proteins Receptors Nerve Growth Factor DrBphP Article opto-RTK 03 medical and health sciences Humans Nerve Growth Factors Receptor Fibroblast Growth Factor Type 1 Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway 030304 developmental biology Tissue Engineering Receptor Protein-Tyrosine Kinases FGFR1 biology.protein 1182 Biochemistry cell and molecular biology BIOSENSORS 3111 Biomedicine MEMBRANE Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | J Mol Biol |
| Popis: | 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 PLC gamma 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. (C) 2020 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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