Quantitative interaction analysis permits molecular insights into functional NOX4 NADPH oxidase heterodimer assembly.

ABSTRACT: Protein-protein interactions critically regulate many biological systems, but quantifying functional assembly of multipass membrane complexes in their native context is still challenging. Here, we combined modeling-assisted protein modification and information from human disease variants with a minimal-size fusion tag, split-luciferase-based approach to probe assembly of the NADPH oxidase 4 (NOX4)-p22^phox enzyme, an integral membrane complex with unresolved structure, which is required for electron transfer and generation of reactive oxygen species (ROS). Integrated analyses of heterodimerization, trafficking, and catalytic activity identified determinants for the NOX4-p22^phox interaction, such as heme incorporation into NOX4 and hot spot residues in transmembrane dom

SUBMITTER: O'Neill S 

PROVIDER: S-EPMC5995528 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature