Inositol Hexaphosphate as an Inhibitor and Potential Regulator of p47^phox Membrane Anchoring.

ABSTRACT: As a key component for NADPH oxidase 2 (NOX2) activation, the peripheral membrane protein p47^phox translocates a cytosolic activating complex to the membrane through its PX domain. This study elucidates a potential regulatory mechanism of p47^phox recruitment and NOX2 activation by inositol hexaphosphate (IP6). Through NMR, fluorescence polarization, and FRET experimental results, IP6 is shown to be capable of breaking the lipid binding and membrane anchoring events of p47^phox-PX with low micromolar potency. Other phosphorylated inositol species such as IP5(1,3,4,5,6), IP4(1,3,4,5), and IP3(1,3,4) show weaker binding and no ability to inhibit lipid interactions in physiological concentration ranges. The low micromolar potency of IP6 inhibition of the p47

SUBMITTER: Develin AM 

PROVIDER: S-EPMC11080064 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature