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OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz

Keen, Alastair C.; Pedersen, Maria Hauge; Lemel, Laura; Scott, Daniel J.; Canals, Meritxell; Littler, Dene R.; Beddoe, Travis; Ono, Yuki; Shi, Lei; Inoue, Asuka; Javitch, Jonathan A.; Lane, J. Robert

OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz Thumbnail


Authors

Alastair C. Keen

Maria Hauge Pedersen

Laura Lemel

Daniel J. Scott

Dene R. Littler

Travis Beddoe

Yuki Ono

Lei Shi

Asuka Inoue

Jonathan A. Javitch

ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
Associate Professor



Abstract

Heterotrimeric G proteins are the main signalling effectors for G protein-coupled receptors. Understanding the distinct functions of different G proteins is key to understanding how their signalling modulates physiological responses. Pertussis toxin, a bacterial AB5 toxin, inhibits Gαi/o G proteins and has proven useful for interrogating inhibitory G protein signalling. Pertussis toxin, however, does not inhibit one member of the inhibitory G protein family, Gαz. The role of Gαz signalling has been neglected largely due to a lack of inhibitors. Recently, the identification of another Pertussis-like AB5 toxin was described. Here we show that this toxin, that we call OZITX, specifically inhibits Gαi/o and Gαz G proteins and that expression of the catalytic S1 subunit is sufficient for this inhibition. We identify mutations that render Gα subunits insensitive to the toxin that, in combination with the toxin, can be used to interrogate the signalling of each inhibitory Gα G protein.

Journal Article Type Article
Acceptance Date Feb 17, 2022
Online Publication Date Mar 23, 2022
Publication Date 2022
Deposit Date Feb 28, 2022
Publicly Available Date Mar 24, 2022
Journal Communications Biology
Electronic ISSN 2399-3642
Peer Reviewed Peer Reviewed
Volume 5
Issue 1
Article Number 256
DOI https://doi.org/10.1038/s42003-022-03191-5
Keywords General Agricultural and Biological Sciences; General Biochemistry, Genetics and Molecular Biology; Medicine (miscellaneous)
Public URL https://nottingham-repository.worktribe.com/output/7529213

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