title: Crystal structure of the maltose transporter in a pretranslocation intermediate state.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Purdue University, Howard Hughes Medical Institute, West Lafayette, IN 47907, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Oldham
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D001665:Binding Sites; D001693:Biological Transport, Active; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008320:Maltose / Q000378:metabolism; D058619:Maltose-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D019897:Periplasm / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; C461639:MalF protein, E coli; C079123:MalG protein, E coli; C489398:MalK protein, E coli; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; C461599:maltose transport system, E coli; D008320:Maltose; D000255:Adenosine Triphosphate