OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz.
journal contributionposted on 2022-05-05, 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.
Article NumberARTN 256
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Science & TechnologyLife Sciences & BiomedicineBiologyMultidisciplinary SciencesLife Sciences & Biomedicine - Other TopicsScience & Technology - Other TopicsNUCLEOTIDE-BINDING PROTEINISLET-ACTIVATING PROTEINADP-RIBOSYLATIONALPHA-SUBUNITHUMAN D1RECEPTORSITECYCLASEIDENTIFICATIONSELECTIVITYGTP-Binding Protein alpha Subunits, Gi-GoHeterotrimeric GTP-Binding ProteinsPertussis ToxinReceptors, G-Protein-CoupledSignal Transduction