Figure 2.

Structure and localization of Pgp in plasma membrane. (A) Pgp is a transmembrane protein with drug-binding pocket localized in the inner leaflet of the plasma membrane, and two NBD localized in cytoplasm. Functional Pgp is localized in cholesterol, sphingomyelin, and GM1 ganglioside-rich membrane microdomains, called lipid rafts, where it is surrounded by fluid phase of the membrane, containing unsaturated fatty acids like DPPC. Pgp is pictured in inward-open (outward closed) conformation ready to bind substrate. The model is based on X-ray analysis⁵⁶ and NMR data from protein data bank (http://www.rcsb.org/). (B) Incorporation of Pluronic into lipid bilayer disrupts lipid rafts, possibly causing conformational changes in Pgp, which results in inhibition of Pgp ATPase and transport activities.