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

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Leopold , A , Pletnev , S & Verkhusha , V V 2020 , ' Bacterial Phytochrome as a Scaffold for Engineering of Receptor Tyrosine Kinases Controlled with Near-Infrared Light ' , Journal of Molecular Biology , vol. 432 , no. 13 , pp. 3749-3760 . https://doi.org/10.1016/j.jmb.2020.04.005

Title: Bacterial Phytochrome as a Scaffold for Engineering of Receptor Tyrosine Kinases Controlled with Near-Infrared Light
Author: Leopold, Anna; Pletnev, Sergei; Verkhusha, Vladislav V.
Contributor: University of Helsinki, Department of Anatomy
University of Helsinki, Department of Anatomy
Date: 2020-06-12
Language: eng
Number of pages: 12
Belongs to series: Journal of Molecular Biology
ISSN: 0022-2836
URI: http://hdl.handle.net/10138/331179
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 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.
Subject: bacteriophytochrome
DrBphP
EGFR
FGFR1
opto-RTK
FLUORESCENT PROTEINS
ACTIVATION
DOMAIN
BIOSENSORS
MEMBRANE
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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