title: Solution structure of the tandem Src homology 3 domains of p47phox in an autoinhibited form.
abstract: The phagocyte NADPH oxidase is a multisubunit enzyme responsible for the generation of superoxide anions (O(2).) that kill invading microorganisms. p47(phox) 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 p47(phox) 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 solution 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 p22(phox).
authors.affiliation: Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogura
authors.forename: Masataka
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Suzuki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Mikio
authors.initials: M
authors.lastname: Kataoka
authors.forename: Hideki
authors.initials: H
authors.lastname: Sumimoto
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D019281:Dimerization; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D010750:Phosphoproteins; D021122:Protein Subunits