title: Allosteric transitions of ATP-binding cassette transporter MsbA studied by the adaptive anisotropic network model.
abstract: The transporter MsbA is a kind of multidrug resistance ATP-binding cassette transporter that can transport lipid A, lipopolysaccharides, and some amphipathic drugs from the cytoplasmic to the periplasmic side of the inner membrane. In this work, we explored the allosteric pathway of MsbA from the inward- to outward-facing states during the substrate transport process with the adaptive anisotropic network model. The results suggest that the allosteric transitions proceed in a coupled way. The large-scale closing motions of the nucleotide-binding domains occur first, accompanied with a twisting motion at the same time, which becomes more obvious in middle and later stages, especially for the later. This twisting motion plays an important role for the rearrangement of transmembrane helices and the opening of transmembrane domains on the periplasmic side that mainly take place in middle and later stages respectively. The topological structure plays an important role in the motion correlations above. The conformational changes of nucleotide-binding domains are propagated to the transmembrane domains via the intracellular helices IH1 and IH2. Additionally, the movement of the transmembrane domains proceeds in a nonrigid body, and the two monomers move in a symmetrical way, which is consistent with the symmetrical structure of MsbA. These results are helpful for understanding the transport mechanism of the ATP-binding cassette exporters.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Xiao Lu
authors.initials: XL
authors.lastname: Xie
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Li
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Yong Xiao
authors.initials: YX
authors.lastname: Yang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Tan
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Xiao Yi
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: College of Science, Yanshan University, Qinhuangdao, 066004, China.
authors.forename: Ji Guo
authors.initials: JG
authors.lastname: Su
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
authors.forename: Cun Xin
authors.initials: CX
authors.lastname: Wang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000465:Algorithms; D016880:Anisotropy; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009038:Motion; D019897:Periplasm / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; C079726:MsbA protein, Bacteria
keywords: ABC transporter; aANM; allosteric pathway; multidrug transport; transmembrane proteins