Conformational and dynamical plasticity in substrate-binding proteins underlies selective transport in ABC importers

University of Groningen, Netherlands
KU Leuven, Belgium
University of Melbourne, Australia
Ludwig Maximilians-Universität München, Germany

Research Article Mar 22, 2019

Cited 12
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Cite this article as: eLife 2019;8:e44652 doi: 10.7554/eLife.44652

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Abstract

Substrate-binding proteins (SBPs) are associated with ATP-binding cassette importers and switch from an open to a closed conformation upon substrate binding, providing specificity for transport. We investigated the effect of substrates on the conformational dynamics of six SBPs and the impact on transport. Using single-molecule FRET, we reveal an unrecognized diversity of plasticity in SBPs. We show that a unique closed SBP conformation does not exist for transported substrates. Instead, SBPs sample a range of conformations that activate transport. Certain non-transported ligands leave the structure largely unaltered or trigger a conformation distinct from that of transported substrates. Intriguingly, in some cases similar SBP conformations are formed by both transported and non-transported ligands. In this case, the inability for transport arises from slow opening of the SBP or the selectivity provided by the translocator. Our results reveal the complex interplay between ligand-SBP interactions, SBP conformational dynamics and substrate transport.

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Author details

Marijn de Boer

Molecular Microscopy Research Group, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Giorgos Gkouridis

Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium

Competing interests
The authors declare that no competing interests exist.
Ruslan Vietrov

Department of Biochemistry, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Stephanie L Begg

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Gea K Schuurman-Wolters

Department of Biochemistry, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Florence Husada

Molecular Microscopy Research Group, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Nikolaos Eleftheriadis

Molecular Microscopy Research Group, University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Bert Poolman

Department of Biochemistry, University of Groningen, Groningen, Netherlands

For correspondence
b.poolman@rug.nl

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1455-531X
Christopher A McDevitt

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia

For correspondence
christopher.mcdevitt@unimelb.edu.au

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1596-4841
Thorben Cordes

Faculty of Biology, Ludwig Maximilians-Universität München, Planegg Martinsried, Germany

For correspondence
cordes@bio.lmu.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8598-5499

Funding

European Commission (638536)

Thorben Cordes

European Molecular Biology Organization (ALF 47-2012)

Giorgos Gkouridis

Deutsche Forschungsgemeinschaft (GRK2062/1 (C03))

Thorben Cordes

Deutsche Forschungsgemeinschaft (SFB863 (A13))

Thorben Cordes

National Health and Medical Research Council (1080784)

Christopher A McDevitt

National Health and Medical Research Council (1122582)

Christopher A McDevitt

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (722.012.012)

Giorgos Gkouridis

European Commission (670578)

Bert Poolman

Australian Research Council (DP170102102)

Christopher A McDevitt

Australian Research Council (FT170100006)

Christopher A McDevitt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

Baron Chanda, University of Wisconsin-Madison, United States

Publication history

Received: December 21, 2018
Accepted: March 22, 2019
Accepted Manuscript published: March 22, 2019 (version 1)
Version of Record published: April 5, 2019 (version 2)

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.