Adenosine triphosphate (ATP)-binding cassette (ABC) transporters convert
chemical energy from ATP hydrolysis to mechanical work for substrate
translocation. They function by alternating between two states, exposing the
substrate-binding site to either side of the membrane. A key question that
remains to be addressed is how substrates initiate the transport cycle. Using
x-ray crystallography, we have captured the maltose transporter in an
intermediate step between the inward- and outward-facing states. We show that
interactions with substrate-loaded maltose-binding protein in the periplasm
induce a partial closure of the MalK dimer in the cytoplasm. ATP binding to this
conformation then promotes progression to the outward-facing state. These
results, interpreted in light of biochemical and functional studies, provide a
structural basis to understand allosteric communication in ABC transporters.
