Single-molecule probing of the conformational homogeneity of the ABC transporter BtuCD.

Autor: Yang M; National Laboratory of Macromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China., Livnat Levanon N; Department of Biochemistry and the Rappaport Institute for Medical Sciences, Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel., Acar B; Department of Chemical Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey., Aykac Fas B; Department of Chemical Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey., Masrati G; Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel., Rose J; Department of Biochemistry and the Rappaport Institute for Medical Sciences, Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel., Ben-Tal N; Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. bental@tauex.tau.ac.il., Haliloglu T; Department of Chemical Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey. halilogt@boun.edu.tr., Zhao Y; National Laboratory of Macromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China., Lewinson O; Department of Biochemistry and the Rappaport Institute for Medical Sciences, Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel. lewinson@technion.ac.il.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2018 Jul; Vol. 14 (7), pp. 715-722. Date of Electronic Publication: 2018 Jun 18.
DOI: 10.1038/s41589-018-0088-2
Abstrakt: ATP-binding cassette (ABC) transporters use the energy of ATP hydrolysis to move molecules through cellular membranes. They are directly linked to human diseases, cancer multidrug resistance, and bacterial virulence. Very little is known of the conformational dynamics of ABC transporters, especially at the single-molecule level. Here, we combine single-molecule spectroscopy and a novel molecular simulation approach to investigate the conformational dynamics of the ABC transporter BtuCD. We observe a single dominant population of molecules in each step of the transport cycle and tight coupling between conformational transitions and ligand binding. We uncover transient conformational changes that allow substrate to enter the transporter. This is followed by a 'squeezing' motion propagating from the extracellular to the intracellular side of the translocation cavity. This coordinated sequence of events provides a mechanism for the unidirectional transport of vitamin B 12 by BtuCD.
Databáze: MEDLINE
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