OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including G alpha(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 AB(5) toxin, inhibits G alpha(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, G alpha(z). The role of G alpha(z) signalling has been neglected largely due to a lack of inhibitors. Recently, the identification of another Pertussis-like AB(5) toxin was described. Here we show that this toxin, that we call OZITX, specifically inhibits G alpha(i/o) and G alpha(z) G proteins and that expression of the catalytic S1 subunit is sufficient for this inhibition. We identify mutations that render G alpha subunits insensitive to the toxin that, in combination with the toxin, can be used to interrogate the signalling of each inhibitory G alpha G protein.