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PMID: 17290225 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 26 ·No. 4 ·2007-02-21 ·Pages 1176-86

Honbou K, Minakami R, Yuzawa S, Takeya R, Suzuki NN, Kamakura S, Sumimoto H, Inagaki F

Abstract

The superoxide-producing phagocyte NADPH oxidase is activated during phagocytosis to destroy ingested microbes. The adaptor protein p40phox 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 p40phox 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.

MeSH Terms
Animals Crystallization HeLa Cells Humans Immunoprecipitation Mice Microscopy, Confocal Models, Molecular NADPH Oxidases/chemistry,metabolism Phagocytosis/genetics,physiology Phagosomes/metabolism Phosphatidylinositol Phosphates/metabolism Phosphoproteins/metabolism Protein Binding Protein Structure, Tertiary
Chemicals
Phosphatidylinositol Phosphates Phosphoproteins neutrophil cytosol factor 67K phosphatidylinositol 3-phosphate NADPH Oxidases NCF4 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Honbou Kazuya
Laboratory of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Minakami Reiko
Yuzawa Satoru
Takeya Ryu
Suzuki Nobuo N
Kamakura Sachiko
Sumimoto Hideki
Inagaki Fuyuhiko
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601561
Published
2007-02-21
Epub
2007-00-08
Pages
1176-86
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1852833
Subset
IM
Databases
PDB
2DYB
External Links
PubMed source DOI: 10.1038/sj.emboj.7601561 PMC Full Text View journal details
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