6a6n

Publication Abstract from PubMed

P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues from their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, largely due to the lack of high-resolution structural information regarding the alternate conformational states of the molecule. Here we report a pair of structures of homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide and an inward-facing apo state, at resolutions of 1.9 A and 3.0 A, respectively. Features that can be clearly visualized at this high resolution include ATP binding with octahedral coordination of Mg(2+); an inner chamber that significantly changes in volume with the aid of tight connections among transmembrane helices (TM) 1, 3, and 6; a glutamate-arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TM1 and TM3, a property that distinguishes multidrug transporters from floppases. These structural elements are proposed to participate in the mechanism of the transporter.

Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1.,Kodan A, Yamaguchi T, Nakatsu T, Matsuoka K, Kimura Y, Ueda K, Kato H Nat Commun. 2019 Jan 8;10(1):88. doi: 10.1038/s41467-018-08007-x. PMID:30622258^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.