Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding

Kazuya Honbou, Reiko Minakami, Satoru Yuzawa, Ryu Takeya, Nobuo N. Suzuki, Sachiko Kamakura, Hideki Sumimoto, Fuyuhiko Inagaki

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


The superoxide-producing phagocyte NADPH oxidase is activated during phagocytosis to destroy ingested microbes. The adaptor protein p40 phox associates via the PB1 domain with the essential oxidase activator p67phox, and is considered to function by recruiting p67phox to phagosomes; in this process, the PX domain of p40 phox binds to phosphatidylinositol 3-phosphate [PtdIns(3)P], a lipid abundant in the phagosomal membrane. Here we show that the PtdIns(3)P-binding activity of p40phox is normally inhibited by the PB1 domain both in vivo and in vitro. The crystal structure of the full-length p40phox reveals that the inhibition is mediated via intramolecular interaction between the PB1 and PX domains. The interface of the p40phox PB1 domain for the PX domain localizes on the opposite side of that for the p67phox PB1 domain, and thus the PB1-mediated PX regulation occurs without preventing the PB1-PB1 association with p67phox.

Original languageEnglish
Pages (from-to)1176-1186
Number of pages11
JournalEMBO Journal
Issue number4
Publication statusPublished - Feb 21 2007

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology


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