title: Two molybdate/tungstate ABC transporters that interact very differently with their substrate binding proteins.
abstract: In all kingdoms of life, ATP Binding Cassette (ABC) transporters participate in many physiological and pathological processes. Despite the diversity of their functions, they have been considered to operate by a largely conserved mechanism. One deviant is the vitamin B12 transporter BtuCD that has been shown to operate by a distinct mechanism. However, it is unknown if this deviation is an exotic example, perhaps arising from the nature of the transported moiety. Here we compared two ABC importers of identical substrate specificity (molybdate/tungstate), and find that their interactions with their substrate binding proteins are utterly different. One system forms a high-affinity, slow-dissociating complex that is destabilized by nucleotide and substrate binding. The other forms a low-affinity, transient complex that is stabilized by ligands. The results highlight significant mechanistic divergence among ABC transporters, even when they share the same substrate specificity. We propose that these differences are correlated with the different folds of the transmembrane domains of ABC transporters.
authors.affiliation: Department of Microbiology, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Vigonsky
authors.forename: Elena
authors.initials: E
authors.lastname: Ovcharenko
authors.forename: Oded
authors.initials: O
authors.lastname: Lewinson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D019611:Archaeoglobus fulgidus; D002850:Chromatography, Gel; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006193:Haemophilus influenzae; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D008958:Models, Molecular; D008982:Molybdenum / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D033902:Periplasmic Binding Proteins / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D013379:Substrate Specificity; D017973:Tungsten Compounds / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; C050021:BtuC peptide, E coli; C050022:BtuD peptide, E coli; D029968:Escherichia coli Proteins; D008081:Liposomes; D046912:Multiprotein Complexes; D033902:Periplasmic Binding Proteins; D017973:Tungsten Compounds; C446048:btuF protein, E coli; C461599:maltose transport system, E coli; C044659:molybdate; D008982:Molybdenum; C045951:tungstate