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

Min Yang, Nurit Livnat Levanon, Burçin Acar, Burcu Aykac Fas, Gal Masrati, Jessica Rose, Nir Ben-Tal, Turkan Haliloglu, Yongfang Zhao, Oded Lewinson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)715-722
Number of pages8
JournalNature Chemical Biology
Volume14
Issue number7
DOIs
StatePublished - 1 Jul 2018

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