title: Alternating access in maltose transporter mediated by rigid-body rotations.
abstract: ATP-binding cassette transporters couple ATP hydrolysis to substrate translocation through an alternating access mechanism, but the nature of the conformational changes in a transport cycle remains elusive. Previously we reported the structure of the maltose transporter MalFGK(2) in an outward-facing conformation in which the transmembrane (TM) helices outline a substrate-binding pocket open toward the periplasmic surface and ATP is poised for hydrolysis along the closed nucleotide-binding dimer interface. Here we report the structure of the nucleotide-free maltose transporter in which the substrate binding pocket is only accessible from the cytoplasm and the nucleotide-binding interface is open. Comparison of the same transporter crystallized in two different conformations reveals that alternating access involves rigid-body rotations of the TM subdomains that are coupled to the closure and opening of the nucleotide-binding domain interface. The comparison also reveals that point mutations enabling binding protein-independent transport line dynamic interfaces in the TM region.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Khare
authors.forename: Michael L
authors.initials: ML
authors.lastname: Oldham
authors.forename: Cedric
authors.initials: C
authors.lastname: Orelle
authors.forename: Amy L
authors.initials: AL
authors.lastname: Davidson
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008320:Maltose / Q000378:metabolism*; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D009154:Mutation; D011487:Protein Conformation
chemical_list: D018528:ATP-Binding Cassette Transporters; D009004:Monosaccharide Transport Proteins; D008320:Maltose