Fig. 5.

Illustration of P450 system protein localization in the ER. Lipid membranes are thought to be segregated into liquid-ordered (l_o) and liquid-disordered domains. The ordered domains (which also are referred to as lipid rafts) tend to be more enriched in cholesterol and SM, tend to pack more tightly, and are more resistant to solubilization by detergents (Diaz-Rohrer et al., 2014). P450 system proteins do not distribute randomly throughout the membrane, but they localize in regions of differing phospholipid composition. P450s and CPR have also been reported to be more closely associated with PE and the anionic phospholipids PS and PI, the phospholipids that surround P450 enzymes. The phospholipid regions with the predominant yellow head groups represent the l_o microdomains with the disordered regions being largely in gray. Cholesterol (aqua) and SM (black) are intercalated into the l_o regions. The anionic phospholipids are indicated by the red polar head groups. CYP1A2 and CPR localize predominantly in the l_o regions, whereas CYP1A1 and CYP2E1 are found mainly in the disordered membranes. CYP2B4 distributes between both regions. The figure also illustrates the tendency of different P450 enzymes to form P450⋅P450 complexes.