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 organization: | Department of Anatomy Faculty of Medicine Medicum University of Helsinki |
Date: | 2020-06-12 |
Language: | eng |
Number of pages: | 12 |
Belongs to series: | Journal of Molecular Biology |
ISSN: | 0022-2836 |
DOI: | https://doi.org/10.1016/j.jmb.2020.04.005 |
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 |
Peer reviewed: | Yes |
Rights: | cc_by_nc_nd |
Usage restriction: | openAccess |
Self-archived version: | acceptedVersion |
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