title: Structural Dynamics of the Heterodimeric ABC Transporter TM287/288 Induced by ATP and Substrate Binding.
abstract: TM287/288 is a heterodimeric ATP-binding cassette (ABC) transporter, which harnesses the energy of ATP binding and hydrolysis at the nucleotide-binding domains (NBDs) to transport a wide variety of molecules through the transmembrane domains (TMDs) by alternating inward- and outward-facing conformations. Here, we conducted multiple 100 ns molecular dynamics simulations of TM287/288 in different ATP- and substrate-bound states to elucidate the effects of ATP and substrate binding. As a result, the binding of two ATP molecules to the NBDs induced the formation of the consensus ATP-binding pocket (ABP2) or the NBD dimerization, whereas these processes did not occur in the presence of a single ATP molecule or when the protein was in its apo state. Moreover, binding of the substrate to the TMDs enhanced the formation of ABP2 through allosteric TMD-NBD communication. Furthermore, in the apo state, α-helical subdomains of the NBDs approached each other, acquiring a conformation with core half-pockets exposed to the solvent, appropriate for ATP binding. We propose a "core-exposed" model for this novel conformation found in the apo state of ABC transporters. These findings provide important insights into the structural dynamics of ABC transporters.
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology , B-62 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Furuta
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology , B-62 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology , B-62 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D000255:Adenosine Triphosphate