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Full‐length p40 phox structure suggests a basis for regulation mechanism of its membrane binding
Author(s) -
Honbou Kazuya,
Minakami Reiko,
Yuzawa Satoru,
Takeya Ryu,
Suzuki Nobuo N,
Kamakura Sachiko,
Sumimoto Hideki,
Inagaki Fuyuhiko
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601561
Subject(s) - library science , graduate students , agency (philosophy) , chinese academy of sciences , political science , sociology , medicine , medical education , computer science , social science , law , china
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 p67 phox , and is considered to function by recruiting p67 phox 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 p40 phox is normally inhibited by the PB1 domain both in vivo and in vitro . The crystal structure of the full‐length p40 phox reveals that the inhibition is mediated via intramolecular interaction between the PB1 and PX domains. The interface of the p40 phox PB1 domain for the PX domain localizes on the opposite side of that for the p67 phox PB1 domain, and thus the PB1‐mediated PX regulation occurs without preventing the PB1–PB1 association with p67 phox .