Structure and Mechanism of a Eukaryotic ABC Multidrug Transporter

Abstract

ATP-binding cassette (ABC) multidrug transporters are membrane proteins which transport various structurally unrelated substrates using the energy of ATP hydrolysis. The precise transport mechanisms of a human ABC multidrug transporter, P-glycoprotein (hP-gp), are not fully understood based on the crystal structure, because of the difficulty of crystallization of hP-gp. Recently, we have determined the crystal structures of a hP-gp homolog, CmABCB1 from Cyanidioschyzon merolae, at 2.6 Å, and its complex with a novel allosteric inhibitor at 2.4 Å. Here, we present how these high resolution structure determinations were achieved, and explain the detailed architecture of the transmembrane domains of CmABCB1.