OZITX, a Pertussis Toxin-like Protein for Occluding Inhibitory G Protein Signalling Including Gα

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Mar 24

PMID 35322196

Authors

Alastair C Keen

Maria Hauge Pedersen

Laura Lemel

Daniel J Scott

Meritxell Canals

Dene R Littler

Travis Beddoe

Yuki Ono

Lei Shi

Asuka Inoue

Jonathan A Javitch

J Robert Lane

Affiliations

Soon will be listed here.

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 AB toxin, inhibits Gα 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, Gα. The role of Gα signalling has been neglected largely due to a lack of inhibitors. Recently, the identification of another Pertussis-like AB toxin was described. Here we show that this toxin, that we call OZITX, specifically inhibits Gα and Gα 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.

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