Reaction chemistry ABC-style.

F or a time, membrane proteins proved intractable to X-ray crystallography. There were difficulties of overexpression and purification, multiple choices of solubilizing detergent that could only be decided by trial and error, unwillingness to crystallize, and often, poor diffraction from resultant crystals. However, the tide now seems to be turning, and in PNAS, Oldham and Chen (1) present an X-ray crystallography study of the entire WT maltose uptake protein from Escherichia coli, in which four different structures are described at commendable 2.2to 2.4-Å resolution. Maltose uptake protein is a well-characterized model (2) for the large ABC transporter family, members of which occur in all living organisms. ABC transporters, whether exporters or importers, display a common architecture consisting of two transmembrane domains (TMDs) involved directly in transport and two nucleotide binding domains (NBDs) that cooperatively hydrolyze ATP (actually MgATP) to power transport (3). Internationally, numerous researchers study ABC transporters because of their wide involvement in human and plant disease and consequent importance in medicine and agriculture. Maltose uptake protein has subunit structure MalGFK2, with GF forming the TMDs and K2 forming the head to tail NBD dimer, with its two ATP binding sites. Bacterial ABC importers use a binding protein that captures the requisite transport substrate from the periplasm and delivers it to the transporter. In the work by Oldham and Chen (1), maltose binding protein is bound to the MalGFK2 complex in its open state, and the justdelivered maltose molecule is clearly seen in the transport pathway at midmembrane.