OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz
Year: 2022
Type: article
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 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.
Source: Communications Biology
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
Institutions: University of Nottingham, Queen's Medical Centre, Monash University, University of Birmingham, University of Copenhagen, New York State Psychiatric Institute, Columbia University, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, La Trobe University, Tohoku University, National Institutes of Health, National Institute on Drug Abuse
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,490
Funders: U.S. Department of Health and Human Services, Research Councils UK, Novo Nordisk Fonden, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, National Institute of Mental Health
OpenAlex ID: W4220692437