Conformational and dynamic plasticity in substrate-binding proteins underlies selective transport in ABC importers
Conformational and dynamic plasticity in substrate-binding proteins underlies selective transport in ABC importers
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DOI：
10.7554/elife.44652
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发表时间：
2019-03-22
期刊：
影响因子：
7.7
通讯作者：
Cordes, Thorben
中科院分区：
文献类型：
--
作者：
de Boer, Marijn;Gouridis, Giorgos;Cordes, Thorben
底物结合蛋白（SBPs）与ATP结合盒输入者相关，并在底物结合时从开放构象转变为闭合构象，为转运提供特异性。我们研究了底物对六种SBPs构象动力学的影响及其对转运的影响。使用单分子FRET，我们揭示了一个未被承认的多样性的可塑性SBPs。我们表明，一个独特的封闭SBP构象不存在运输基板。相反，SBPs对激活运输的一系列构象进行采样。某些非转运配体的结构基本上保持不变，或触发不同于转运底物的构象。有趣的是，在某些情况下，类似的SBP构象是由转运和非转运配体形成的。在这种情况下，不能运输是由于SBP的缓慢开放或转运蛋白提供的选择性。我们的研究结果揭示了配体SBP相互作用，SBP构象动力学和底物转运之间的复杂的相互作用。
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 nontransported 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.