Journal article

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

Marijn de Boer, Giorgos Gouridis, Ruslan Vietrov, Stephanie L Begg, Gea K Schuurman-Wolters, Florence Husada, Nikolaos Eleftheriadis, Bert Poolman, Christopher A McDevit, Thorben Cordes



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. Int..

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Awarded by European Commission

Awarded by Deutsche Forschungsgemeinschaft

Awarded by National Health and Medical Research Council

Awarded by Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Awarded by H2020 European Research Council ERC

Awarded by Australian Research Council

Awarded by European Molecular Biology Organization

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.