Conformation of membrane-inserted P-glycoprotein

Background The human genome codes for 49 members of the large ABC protein family. Most of them are membrane transporters. The first structures of exporters have been solved in recent years. Although a remarkable achievement, some uncertainty remained with respect to the physiological conformation of the transporter, which seems not to be fully compatible with all biochemical evidence. During crystallization, the transporter is extracted from its native membrane environment and solubilized by surfactants. This procedure might have influenced the transporters’ conformation and lead to the structures observed in the crystals. We focus on the multidrug resistance transporter P-glycoprotein, which prevents xenotoxic compounds from entering the body and from penetrating into the brain, and confers resistance to chemotherapy.