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

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posted on 05.05.2022, 07:00 authored by Alastair C Keen, Maria Hauge Pedersen, Laura Lemel, Daniel J Scott, Meritxell Canals, Dene R Littler, Travis BeddoeTravis Beddoe, Yuki Ono, Lei Shi, Asuka Inoue, Jonathan A Javitch, J Robert Lane
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.

History

Publication Date

01/01/2022

Journal

Communications Biology

Volume

5

Issue

1

Article Number

ARTN 256

Pagination

10p.

Publisher

Springer Nature

ISSN

2399-3642

Rights Statement

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/