The ATP-switch mechanism (Higgins and Linton, 2004; Linton and Higgins, 2007). The transport cycle is started by binding of a substrate (purple cross) to a highaffinity
pocket formed by the TMDs (blue and yellow pentagon). Subsequently, a conformational change is transmitted to the NBDs (green and red), facilitating ATP (orange oval)
binding and closed NBD-dimer formation. The closed NBD dimer induces on its turn a major conformational change in the TMDs, with TMDs rotating and opening toward the
outside, initiating substrate translocation (step II). ATP hydrolysis initiates dissolution of the closed NBD dimer, resulting in further conformational changes in the TMDs (step III).
Finally, phosphate and ADP release restores the transporter to the open NBD-dimer conformation (step IV).