The Maltose ABC Transporter: Where Structure Meets Function

ATP-binding cassette (ABC) transporters mediate active transport of a variety of substrates across biological membranes. The long studied maltose importer from Escherichia coli has provided a wealth of biochemical and genetic information, making it an attractive target for structure determination. The maltose transporter is a complex composed of a heterodimer of transmembrane subunits and a nucleotide-binding subunit homodimer that together function in concert with a periplasmic-binding protein, responsible for delivery of maltose to the transporter. The complex has now been crystallized in multiple states along the translocation pathway. Functional studies were key for stabilizing the transporter in these conformational states, validating the structures and understanding the molecular mechanism of transport. ATP hydrolysis and substrate transport are coupled via concerted conformational changes spanning the bilayer that result in alternating access of the substrate-binding site to either side of the membrane. Although the detailed dynamics of the complex remain to be revealed, we illustrate here how the interplay between biochemical, biophysical, and structural studies established the maltose transporter as one of the best characterized proteins of the ABC family. While many of these molecular insights are relevant to the entire ABC transporter family, some mechanistic features may differ between subclasses, highlighting the extraordinary diversity of ABC proteins and the need for further structure/function analyses.