OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including Gα z .

Autor: Keen AC; 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.; Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, Nottingham, UK., Pedersen MH; Departments of Psychiatry and Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.; NNF Center for Basic Metabolic Research, Section for Metabolic Receptology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Lemel L; Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.; Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, Nottingham, UK., Scott DJ; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, 3052, Australia.; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, 3052, VIC, 3052, Australia., Canals M; Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.; Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, Nottingham, UK., Littler DR; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3052, Australia., Beddoe T; Department of Animal, Plant and Soil Science and Centre for AgriBioscience, La Trobe University, Bundoora, VIC, 3086, Australia., Ono Y; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan., Shi L; Computational Chemistry and Molecular Biophysics Section, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, Baltimore, MD, USA., Inoue A; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan., Javitch JA; Departments of Psychiatry and Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. Jonathan.Javitch@nyspi.columbia.edu.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Jonathan.Javitch@nyspi.columbia.edu., Lane JR; Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK. rob.lane@nottingham.ac.uk.; Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, Nottingham, UK. rob.lane@nottingham.ac.uk.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Mar 23; Vol. 5 (1), pp. 256. Date of Electronic Publication: 2022 Mar 23.
DOI: 10.1038/s42003-022-03191-5
Abstrakt: 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 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 AB 5 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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