Chapter 151 - PX Domains

Abstract

The function of several PX domain-containing proteins is reasonably well understood, although the exact role fulfilled by the PX domain is not yet well defined. Tht phox proteins, after which the PX domain was named, are subunits of the NADPH oxidase, the heme-containing enzyme responsible for superoxide production and killing of microorganisms by phagocytic cells. In resting phagocytes, the inactive NADPH oxidase is separated into a set of cytoplasmic subunits including p47 phox , p67 phox , and p40 phox and a membrane-bound heme-containing flavocytochrome b558, which consists of gp91 phox and p22 phox . Upon phagocyte activation, the cytoplasmic components dock with the membrane-bound subunits to form a catalytically active enzyme that can transfer electrons from NADPH to oxygen to form reactive oxygen species (ROS), such as superoxide . PX domains join an expanding family of phosphoinositide-binding domains that includes C2 domains, PH domains, FYVE domains, ENTH domains, and tubby domains. The large differences in structure between these domains suggest that their lipid-binding function arose through the convergent evolution of different structures for the same biological function of lipid binding. It will be important for future work to further examine the structural foundation for lipid binding specificity by PX domains, and explore how their lipid-binding ability contributes to the overall function of PX domain-containing molecules.