Heterodimeric ABC exporters exhibit the following major conformations: IF with separated NBDs with no nucleotide bound (state 0), IF with partially contacting NBDs and one nucleotide bound to the degenerate site or two nucleotides bound (states 1a and 1b, respectively), OF with closed NBDs and two nucleotides bound (state 2) and stably closed NBDs with a nucleotide trapped at the consensus site in its pre-hydrolysis (state 3) or post-hydrolysis (state 4) state. State 0 is rare and not part of the transport cycle. In state 1, the bound nucleotide does not directly bridge the NBD interface, but causes cross-NBD interactions via the D-loops in an allosteric fashion. Transition from state 1a via state 1b to state 2 is reversible and state 2 is stabilized by nucleotide sandwiching at the NBD interface. Full NBD closure (state 2) is required to initiate ATP hydrolysis at the consensus site. During the hydrolysis reaction, which is an irreversible process, the transporter adopts first a pre-hydrolysis state (state 3), then a post-hydrolysis state (state 4) and upon completion of the ATP hydrolysis reverts to the IF state with one ATP bound at the degenerate site (state 1a). The Walker B E-to-Q mutation in the consensus site and nucleotide trapping by vanadate stabilize the pre- and post-hydrolytic transition state, respectively, and thereby OF states 3 and 4 are populated.