Fig. 4: The MRP2 transport cycle.

A In the absence of substrate, MRP2 rests in an auto-inhibited state. Colored as in Fig. 1B. Dotted magenta lines represent unresolved regions of R domain. In this state, ATP-binding does not induce NBD dimerization, but rather stabilizes R domain in the auto-inhibiting position. B Substrate displaces R domain from the auto-inhibited conformation. C Substrate is released in the NBD-dimerized conformation.