Hassane Mchaourab
Last active: 4/3/2018

Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter.

Mishra S, Verhalen B, Stein RA, Wen PC, Tajkhorshid E, Mchaourab HS
Elife. 2014 3: e02740

PMID: 24837547 · PMCID: PMC4046567 · DOI:10.7554/eLife.02740

Multidrug ATP binding cassette (ABC) exporters are ubiquitous ABC transporters that extrude cytotoxic molecules across cell membranes. Despite recent progress in structure determination of these transporters, the conformational motion that transduces the energy of ATP hydrolysis to the work of substrate translocation remains undefined. Here, we have investigated the conformational cycle of BmrCD, a representative of the heterodimer family of ABC exporters that have an intrinsically impaired nucleotide binding site. We measured distances between pairs of spin labels monitoring the movement of the nucleotide binding (NBD) and transmembrane domains (TMD). The results expose previously unobserved structural intermediates of the NBDs arising from asymmetric configuration of catalytically inequivalent nucleotide binding sites. The two-state transition of the TMD, from an inward- to an outward-facing conformation, is driven exclusively by ATP hydrolysis. These findings provide direct evidence of divergence in the mechanism of ABC exporters.DOI: http://dx.doi.org/10.7554/eLife.02740.001.

Copyright © 2014, Mishra et al.

MeSH Terms (13)

Adenosine Triphosphate ATP-Binding Cassette Transporters Carrier Proteins Catalytic Domain Cell Membrane Cloning, Molecular Gene Expression Regulation Hydrolysis Molecular Dynamics Simulation Nanotechnology Nucleotides Protein Conformation Protein Multimerization

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