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

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.

Citation

Keen, A. C., Pedersen, M. H., Lemel, L., Scott, D. J., Canals, M., Littler, D. R., Beddoe, T., Ono, Y., Shi, L., Inoue, A., Javitch, J. A., & Lane, J. R. (2022). OZITX, A pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz. Communications Biology, 5(1), Article 256. https://doi.org/10.1038/s42003-022-03191-5

• 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
• Publisher: Nature Publishing Group
• 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