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Assembly of the phagocyte NADPH oxidase

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Abstract

Stimulated phagocytes undergo a burst in respiration whereby molecular oxygen is converted to superoxide anion through the action of an NADPH-dependent oxidase. The multicomponent phagocyte oxidase is unassembled and inactive in resting cells but assembles at the plasma or phagosomal membrane upon phagocyte activation. Oxidase components include flavocytochrome b558, an integral membrane heterodimer comprised of gp91phox and p22phox, and three cytosolic proteins, p47phox, p67phox, and Rac1 or Rac2, depending on the species and phagocytic cell. In a sense, the phagocyte oxidase is spatially regulated, with critical elements segregated in the membrane and cytosol but ready to undergo nearly immediate assembly and activation in response to stimulation. To achieve such spatial regulation, the individual components in the resting phagocyte adopt conformations that mask potentially interactive structural domains that might mediate productive intermolecular associations and oxidase assembly. In response to stimulation, post-translational modifications of the oxidase components release these constraints and thereby render potential interfaces accessible and interactive, resulting in translocation of the cytosolic elements to the membrane where the functional oxidase is assembled and active. This review summarizes data on the structural features of the phagocyte oxidase components and on the agonist-dependent conformational rearrangements that contribute to oxidase assembly and activation.

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Acknowledgements

Work in the Nauseef laboratory is supported by the National Institutes of Health (AI34879, HL53592, and AI44642) and by a Merit Review Grant from the Department of Veterans Affairs.

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  1. Inflammation Program and Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, D160 MTF, 2501 Crosspark Road, Coralville, IA 52241, USA

    William M. Nauseef

  2. Department of Veterans Affairs, Iowa City VA Medical Center, Iowa City, Iowa, USA

    William M. Nauseef

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Nauseef, W.M. Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol 122, 277–291 (2004). https://doi.org/10.1007/s00418-004-0679-8

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