Fig. 7: Transport cycle of Pdr5.
From: Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5
The substrate (in this case, rhodamine 6G) enters the cavity between the transmembrane domains from the cytoplasmic side when Pdr5 is in inward-facing conformation. ADP remaining in the catalytic site from the previous hydrolysis step is exchanged for ATP. ATP binding triggers a conformation change in Pdr5 from inward- to outward-facing, whereby the substrate is pushed through the substrate channel and released into the extracellular medium. Upon nucleotide hydrolysis, the transporter reverts to inward-facing conformation, ready to receive another molecule of substrate. In cellular conditions, an ATP molecule remains bound to the inactive site throughout the cycle. The asymmetric nature of nucleotide hydrolysis means that one half of Pdr5 makes a larger conformational move than the other. Abbreviations: ECD, extracellular domain; NBD, nucleotide-binding domain; R6G, rhodamine 6G; TMD, transmembrane domain.
