Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Commun Biol. 2022 Mar 23;5(1):256. doi: 10.1038/s42003-022-03191-5.
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.
异三聚体 G 蛋白是 G 蛋白偶联受体的主要信号效应物。了解不同 G 蛋白的独特功能对于理解它们的信号如何调节生理反应至关重要。百日咳毒素是一种细菌 AB 毒素，可抑制 Gα G 蛋白，已被证明对抑制性 G 蛋白信号的研究很有用。然而，百日咳毒素并不能抑制抑制性 G 蛋白家族的一个成员，即 Gα。由于缺乏抑制剂，Gα 信号的作用在很大程度上被忽视了。最近，另一种类似百日咳的 AB 毒素被鉴定出来。在这里，我们表明这种毒素，我们称之为 OZITX，特异性地抑制 Gα 和 Gα G 蛋白，并且表达催化 S1 亚基足以抑制这种作用。我们确定了使 Gα 亚基对毒素不敏感的突变，这些突变与毒素结合使用，可以用来研究每个抑制性 Gα G 蛋白的信号。
