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1535206 
Journal Article 
The NOXO1 beta PX Domain Preferentially Targets PtdIns(4,5)P-2 and PtdIns(3,4,5)P-3 
Davis, NY; Mcphail, LC; Horita, DA 
2012 
Yes 
Journal of Molecular Biology
ISSN: 0022-2836
EISSN: 1089-8638 
417 
5 
440-453 
English 
22342885 
WOS:000302446700006 
NOXO1β [NOXO1 (Nox organizer 1) β] 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. NOXO1β is targeted to membranes through an N-terminal PX (phox homology) domain. We have used NMR spectroscopy to solve the structure of the NOXO1β PX domain and surface plasmon resonance (SPR) to assess phospholipid specificity. The solution structure of the NOXO1β PX domain shows greatest similarity to that of the phosphatidylinositol 3-kinase-C2α 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)P(2) and PtdIns(3,4,5)P(3) as preferred targets of NOXO1β 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)P(2) or PtdIns(3,4,5)P(2) may serve to recruit NOXO1β and activate Nox1. 
NMR spectroscopy; reactive oxygen species; Nox1; protein lipid interactions; phosphatidylinositol