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

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 Gα_i/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, Gα_z. The role of Gα_z 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 Gα_i/o and Gα_z 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.