How are the ABC transporters energized?

Abstract

ATP-binding cassette (ABC) transporters are probably the most common as well as the most wide-spread active transport systems. This family includes many bacterial transporters that either export complex molecules (lipids, polysaccharides, or proteins), or import small nutrients in cooperation with the soluble solute-binding proteins (e.g., the maltose and histidine transport systems of Escherichia coli), as well as such human proteins as the cystic fibrosis transmembrane conductance regulator and the P-glycoprotein that pumps out many anticancer agents. Each transport complex usually contains four domains or subunits, two transmembrane domains each typically containing six transmembrane helices, and two ATPase domains (Fig. 1). The sequence of ABC or ATPase domains always contains the characteristic Walker A and B motifs that are involved in ATP binding (1), but the intervening section between these two motifs is usually longer here than in other ATP-binding enzymes. It ends in a unique motif called LSGGQ motif, C motif, or “signature motif,” because it is present in all ABC subunits, but usually not in other ATPases. Although ATP hydrolysis is clearly the driving force for active transport by ABC transporters, it was not clear how it was coupled to the transmembrane transport of solutes. In this issue of PNAS, Fetsch and Davidson (2) report results that indicate how the two ATPase domains collaborate in ATP hydrolysis, and suggest how this is likely to be coupled to solute transport.