TY - JOUR
T1 - Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1)
AU - Yamamoto, Asataro
AU - Kami, Keiichiro
AU - Takeya, Ryu
AU - Sumimoto, Hideki
N1 - Funding Information:
We are grateful to Yohko Kage (Kyushu University and JST), Miki Matsuo (Kyushu University), Natsuko Yoshiura (Kyushu University), and Namiko Kubo (Kyushu University and JST) for technical assistance, and to Minako Nishino (Kyushu University and JST) for secretarial assistance. This work was supported in part by Grants-in-Aid for Scientific Research and National Project on Protein Structural and Functional Analyses from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by CREST of JST (Japan Science and Technology Agency) and BIRD of JST.
PY - 2007/1/12
Y1 - 2007/1/12
N2 - NADPH oxidase organizer 1 (Noxo1), harboring a PX domain, two SH3 domains, and a proline-rich region (PRR), participates in activation of superoxide-producing Nox-family NADPH oxidases. Here, we show that Noxo1 supports superoxide production in a cell-free system for gp91phox/Nox2 activation by arachidonic acid. This lipid enhances an SH3-mediated binding of Noxo1 to p22phox, a protein complexed with Nox oxidases; the binding is known to be required for Nox activation. We also demonstrate that the bis-SH3 domain directly interacts with the Noxo1 PRR. The interaction appears to prevent the bis-SH3 domain and PRR from binding to their target proteins; disruption of the intramolecular interaction facilitates Noxo1 binding to p22phox and also allows the PRR to associate with the Nox activator Noxa1, which association is crucial for Nox activation as well. These findings suggest that Nox activation involves a conformational change leading to disruption of the bis-SH3-PRR interaction in Noxo1.
AB - NADPH oxidase organizer 1 (Noxo1), harboring a PX domain, two SH3 domains, and a proline-rich region (PRR), participates in activation of superoxide-producing Nox-family NADPH oxidases. Here, we show that Noxo1 supports superoxide production in a cell-free system for gp91phox/Nox2 activation by arachidonic acid. This lipid enhances an SH3-mediated binding of Noxo1 to p22phox, a protein complexed with Nox oxidases; the binding is known to be required for Nox activation. We also demonstrate that the bis-SH3 domain directly interacts with the Noxo1 PRR. The interaction appears to prevent the bis-SH3 domain and PRR from binding to their target proteins; disruption of the intramolecular interaction facilitates Noxo1 binding to p22phox and also allows the PRR to associate with the Nox activator Noxa1, which association is crucial for Nox activation as well. These findings suggest that Nox activation involves a conformational change leading to disruption of the bis-SH3-PRR interaction in Noxo1.
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U2 - 10.1016/j.bbrc.2006.11.060
DO - 10.1016/j.bbrc.2006.11.060
M3 - Article
C2 - 17126813
AN - SCOPUS:33751512270
SN - 0006-291X
VL - 352
SP - 560
EP - 565
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -