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

M De Boer; G Gouridis; R Vietrov; SL Begg; GK Schuurman-Wolters; F Husada; N Eleftheriadis; B Poolman; CA McDevitt; T Cordes

Journal article

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

M De Boer, G Gouridis, R Vietrov, SL Begg, GK Schuurman-Wolters, F Husada, N Eleftheriadis, B Poolman, CA McDevitt, T Cordes

Elife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019

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. In..

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University of Melbourne Researchers

Stephanie Neville Author

Christopher McDevitt Author

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Grants

Awarded by European Commission

Funding Acknowledgements

European Commission 638536 Thorben Cordesr Deutsche Forschungsgemeinschaft GRK2062/1 (C03) Thorben Cordesr Deutsche Forschungsgemeinschaft SFB863 (A13) Thorben Cordesr National Health and Medical Research Council 1080784 Christopher A McDevittr National Health and Medical Research Council 1122582 Christopher A McDevittr Nederlandse Organisatie voor Wetenschappelijk Onderzoek 722.012.012 Giorgos Gouridisr H2020 European Research Council ERC Advanced 670578 Bert Poolmanr Australian Research Council DP170102102 Christopher A McDevittr Australian Research Council FT170100006 Christopher A McDevittr European Molecular Biology Organization ALF 47-2012 Giorgos Gouridisr The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.