Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record.

ABC transporters comprise a large, diverse, and ubiquitous superfamily of membrane active transporters. Their core architecture is a dimer of dimers, comprising two transmembrane domains that bind substrate and form the channel, and two ATP-binding cassettes, which bind and hydrolyze ATP to energize the translocase function. The prevailing paradigm for the ABC transport mechanism is the Switch Model, in which the nucleotide binding domains are proposed to dimerise upon binding of two ATP molecules, and thence dissociate upon sequential hydrolysis of the ATP. This idea appears consistent with crystal structures of both isolated subunits and whole transporters, as well as with a significant body of biochemical data. Nonetheless, an alternative Constant Contact Model has been proposed, in which the nucleotide binding domains do not fully dissociate, and ATP hydrolysis occurs alternately at each of the two active sites. Here, we review the biochemical and biophysical data relating to the ABC catalytic mechanism, to show how they may be construed as consistent with a Constant Contact Model, and to assess to what extent they support the Switch Model.