The NOXO1尾 PX Domain Preferentially Targets PtdIns(4,5)P₂ and PtdIns(3,4,5)P₃

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• 作者：Nicole Y. Davis ; Linda C. McPhail ; David A. Horita ; ^{dhorita@wakehealth.edu}
• 关键词：CISK ; cytokine-independent survival kinase ; PI3K ; phosphatidylinositol 3-kinase ; Nox1 ; NADPH oxidase 1 ; ROS ; reactive oxygen species ; SPR ; surface plasmon resonance ; NOE ; nuclear Overhauser enhancement ; PC ; phosphatidylcholine ; PE ; phosphatidylethanolamin
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 期刊代码：102_00222836
• 类别：imm
• 出版时间：13 April, 2012
• 卷：417
• 期：5
• 页码：440-453
• 文件大小：1576 K

摘要

NOXO1尾 [NOXO1 (Nox organizer 1) 尾] is a cytosolic protein that, in conjunction with NOXA1 (Nox activator 1), regulates generation of reactive oxygen species by the NADPH oxidase 1 (Nox1) enzyme complex. NOXO1尾 is targeted to membranes through an N-terminal PX (phox homology) domain. We have used NMR spectroscopy to solve the structure of the NOXO1尾 PX domain and surface plasmon resonance (SPR) to assess phospholipid specificity. The solution structure of the NOXO1尾 PX domain shows greatest similarity to that of the phosphatidylinositol 3-kinase-C2伪 PX domain with regard to the positions and types of residues that are predicted to interact with phosphatidylinositol phosphate (PtdInsP) head groups. SPR experiments identify PtdIns(4,5)P₂ and PtdIns(3,4,5)P₃ as preferred targets of NOXO1尾 PX. These findings contrast with previous lipid overlay experiments showing strongest binding to monophosphorylated PtdInsP and phosphatidylserine. Our data suggest that localized membrane accumulation of PtdIns(4,5)P₂ or PtdIns(3,4,5)P₂ may serve to recruit NOXO1尾 and activate Nox1.