Mutations in the PX-SH3A linker of p47phox decouple PI(3,4)P2 binding from NADPH oxidase activation.

ABSTRACT: NADPH oxidase is essential in the human innate immune response. p47 (phox), a cytosolic NADPH oxidase component, plays a regulatory role in the activation of NADPH oxidase. Our manipulation of p47 (phox) by mutation and amino acid deletion shows that the linker region between the PX and N-terminal SH3 domain plays a role in blocking the binding of the phosphoinositide 3,4-bisphosphate [PI(3,4)P2], a lipid second messenger generated upon neutrophil activation. Replacement of linker residues 151-158 with glycine alters NMR-measured spin lattice relaxation rates and sedimentation velocity compared to those of the wild-type protein, suggesting that the PX domain is released from its autoinhibited conformation. Liposome binding and surface plasmon resonance experiments confirm this result, show

SUBMITTER: Shen K 

PROVIDER: S-EPMC2745045 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature