title: Simulation of the coupling between nucleotide binding and transmembrane domains in the ATP binding cassette transporter BtuCD.
abstract: The nucleotide-induced structural rearrangements in ATP binding cassette (ABC) transporters, leading to substrate translocation, are largely unknown. We have modeled nucleotide binding and release in the vitamin B(12) importer BtuCD using perturbed elastic network calculations and biased molecular dynamics simulations. Both models predict that nucleotide release decreases the tilt between the two transmembrane domains and opens the cytoplasmic gate. Nucleotide binding has the opposite effect. The observed coupling may be relevant for all ABC transporters because of the conservation of nucleotide binding domains and the shared role of ATP in ABC transporters. The rearrangements in the cytoplasmic gate region do not provide enough space for B(12) to diffuse from the transporter pore into the cytoplasm, which could suggest that peristaltic forces are needed to exclude B(12) from the transporter pore.
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Sonne
authors.forename: Christian
authors.initials: C
authors.lastname: Kandt
authors.forename: Günther H
authors.initials: GH
authors.lastname: Peters
authors.forename: Flemming Y
authors.initials: FY
authors.lastname: Hansen
authors.forename: Morten Ø
authors.initials: MØ
authors.lastname: Jensen
authors.forename: D Peter
authors.initials: DP
authors.lastname: Tieleman
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014805:Vitamin B 12 / Q000737:chemistry*
chemical_list: D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; D014805:Vitamin B 12