4.7 Article

OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including Gαz

Journal

COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03191-5

Keywords

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Funding

  1. National Health and Medical Research Council (NHMRC, Australia) [1049564]
  2. Schaefer Research Scholars Program Award (Columbia University, New York, USA)
  3. Biotechnology and Biological Sciences Research Council [BB/T013966/1]
  4. National Institute of Health (NIH) [MH54137]

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Understanding the signaling of heterotrimeric G proteins is crucial for understanding physiological responses. Pertussis toxin has been widely used to inhibit G alpha(i/o) G proteins, but its effectiveness against G alpha(z) has been limited. A recently discovered toxin, OZITX, has been found to specifically inhibit both G alpha(i/o) and G alpha(z) G proteins, providing a new tool to study their signaling.
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.

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