The domain organization of p67, a protein required for activation of the superoxide-producing NADPH oxidase in phagocytes

Satoru Yuzawa, Kei Miyano, Kazuya Honbou, Fuyuhiko Inagaki, Hideki Sumimoto

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation of the oxidase, the multidomain protein p67phoxplays a central role: it translocates to the membrane as a ternary complex with p47phoxand p40phox, and interacts with the small GTPase Rac to assemble with the membrane-integrated catalytic protein gp91phox, leading to superoxide production. Here we show, using small-angle X-ray scattering (SAXS) analysis, that p67phoxadopts an elongated conformation when it exists not only as a monomer but also as the heterotrimer. Although p67phoxharbors an N-terminal TPR domain for binding to Rac and a p40phox-interacting PB1 domain, followed by an SH3 domain that associates with p47phox, the present model suggests that no or few apparent associations occur between the domains. The positions of the protein-interaction domains in p67 phoxcontribute to activation of the phagocyte NADPH oxidase: the first SH3 domain that is located between the TPR and PB1 domains positively regulates oxidase activation only when it is present at the correct position; the PB1 domain placed at this SH3 domain position inhibits the oxidase by interacting with p40phox.

Original languageEnglish
Pages (from-to)543-555
Number of pages13
JournalJournal of Innate Immunity
Volume1
Issue number6
DOIs
Publication statusPublished - Oct 1 2009

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src Homology Domains
NADPH Oxidase
Phagocytes
Superoxides
Oxidoreductases
Protein Interaction Domains and Motifs
Proteins
Membranes
Monomeric GTP-Binding Proteins
Phagocytosis
Innate Immunity
Oxidants
X-Rays
neutrophil cytosol factor 40K

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Cite this

The domain organization of p67, a protein required for activation of the superoxide-producing NADPH oxidase in phagocytes. / Yuzawa, Satoru; Miyano, Kei; Honbou, Kazuya; Inagaki, Fuyuhiko; Sumimoto, Hideki.

In: Journal of Innate Immunity, Vol. 1, No. 6, 01.10.2009, p. 543-555.

Research output: Contribution to journalArticle

Yuzawa, Satoru ; Miyano, Kei ; Honbou, Kazuya ; Inagaki, Fuyuhiko ; Sumimoto, Hideki. / The domain organization of p67, a protein required for activation of the superoxide-producing NADPH oxidase in phagocytes. In: Journal of Innate Immunity. 2009 ; Vol. 1, No. 6. pp. 543-555.
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