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The NADPH Oxidase Activator p67phox and Its Related Proteins

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NADPH Oxidases Revisited: From Function to Structure

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Abstract

The Nox family NADPH oxidases can be divided into two groups based on the presence or absence of the Ca2+-binding EF-hand motif in the N-terminal cytoplasmic region. Members of the former group can be activated via direct interaction with Ca2+, the cytosolic concentration of which is elevated upon cell stimulation. On the other hand, activation machineries for EF-hand motif-deficient oxidases, which have evolved in animals and fungi, consist of the small GTPase Rac and its binding partner such as p67phox and its homologous proteins. The EF-hand-free phagocyte oxidase Nox2, dormant in resting cells, becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. In this process, the essential Nox2 activator p67phox translocates via collaboration with its constitutively-binding proteins p47phox and p40phox from the cytosol to the phagosomal membrane, and interacts there with independently-recruited, GTP-bound Rac to induce a conformational change of Nox2 for superoxide production. Similarly, the p67phox-related proteins NoxA1 and NoxR associate with Rac–GTP to activate the non-phagocytic oxidase Nox1 and the fungal oxidases NoxA and NoxB, respectively. Here we describe how p67phox as well as its homologues functions in activation of EF-hand-independent oxidases at the molecular level.

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Acknowledgements

This work was supported in part by KAKENHI Grant (21H02698) and Grant-in-Aid for Transformative Research Areas [A] (21H05267) from JSPS (Japan Society for the Promotion of Science).

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Authors and Affiliations

  1. Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Hideki Sumimoto, Akira Kohda, Junya Hayase & Sachiko Kamakura

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  1. Hideki Sumimoto
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  2. Akira Kohda
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  3. Junya Hayase
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  4. Sachiko Kamakura
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Correspondence to Hideki Sumimoto .

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  1. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Edgar Pick

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Sumimoto, H., Kohda, A., Hayase, J., Kamakura, S. (2023). The NADPH Oxidase Activator p67phox and Its Related Proteins. In: Pick, E. (eds) NADPH Oxidases Revisited: From Function to Structure. Springer, Cham. https://doi.org/10.1007/978-3-031-23752-2_16

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