Solution structure of the tandem Src homology 3 domains of p47 phox in an autoinhibited form

Satoru Yuzawa, Kenji Ogura, Masataka Horiuchi, Nobuo N. Suzuki, Yuko Fujioka, Mikio Kataoka, Hideki Sumimoto, Fuyuhiko Inagaki

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Abstract

The phagocyte NADPH oxidase is a multisubunit enzyme responsible for the generation of superoxide anions (O2.-) that kill invading microorganisms. p47phox is a cytosolic subunit of the phagocyte NADPH oxidase, which plays a crucial role in the assembly of the activated NADPH oxidase complex. The molecular shapes of the p47phox tandem SH3 domains either with or without a polybasic/autoinhibitory region (PBR/AIR) at the C terminus were studied using small angle x-ray scattering. The tandem SH3 domains with PBR/AIR formed a compact globular structure, whereas the tandem SH3 domains lacking the PBR/AIR formed an elongated structure. Alignment anisotropy analysis by NMR based on the residual dipolar couplings revealed that the tandem SH3 domains with PBR/AIR were in good agreement with a globular module corresponding to the split half of the intertwisted dimer in crystalline state. The structure of the globular module was elucidated to represent a 1solution structure of the tandem SH3 domain in the autoinhibited form, where the PBR/AIR bundled the tandem SH3 domains and the linker forming a closed structure. Once PBR/AIR is released by phosphorylation, rearrangements of the SH3 domains may occur, forming an open structure that binds to the cytoplasmic proline-rich region of membrane-bound p22phox.

Original languageEnglish
Pages (from-to)29752-29760
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
Publication statusPublished - Jul 9 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yuzawa, S., Ogura, K., Horiuchi, M., Suzuki, N. N., Fujioka, Y., Kataoka, M., Sumimoto, H., & Inagaki, F. (2004). Solution structure of the tandem Src homology 3 domains of p47 phox in an autoinhibited form. Journal of Biological Chemistry, 279(28), 29752-29760. https://doi.org/10.1074/jbc.M401457200