The multi-structural feature of the multidrug resistance gene product p-glycoprotein: Implications for its mechanism of action (Hypothesis)

Abstract

P-glycoprotein is a member of the ATP-binding cassette (ABC) transport superfamily. It plays an important role in the development of multidrug resistance in cancers by effluxing a wide variety of anticancer drugs. A large amount of information on the structure and function of P-glycoprotein has been accumulated over recent years from studies using molecular, biochemical, and biophysical approaches. It remains unclear, however, how this protein folds in membranes and how it transports such a wide variety of hydrophobic compounds. This paper highlights the recent progress in the structural and biogenesis aspects of P-glycoprotein. A model mechanism of P-glycoprotein action is proposed as a hypothesis that is based on recent progress in studying the topological folding of P-glycoprotein.