Institute for Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
Institute for Biochemistry, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
Nat Commun. 2016 Dec 22;7:13864. doi: 10.1038/ncomms13864.
ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain. Based on these results, we propose a model for the coupled ATPase-adenylate kinase mechanism, involving the canonical and an additional nucleotide-binding site. We extend these findings to other prokaryotic ABC exporters, namely LmrA and TmrAB, suggesting that the coupled activities are a general feature of ABC exporters.
三磷酸腺苷结合盒（ABC）转运蛋白是一类整合膜蛋白超家族，通过三磷酸腺苷（ATP）水解催化底物跨膜转运。在这里，我们通过核苷酸周转和基于 P 固体核磁共振波谱的结合研究表明，ABC 外排泵和脂多糖翻转酶 MsbA 可以将 ATP 水解与腺苷酸激酶活性偶联，其中 ADP 转化为 AMP 和 ATP。单点突变表明，ATP 酶和腺苷酸激酶机制都与核苷酸结合域的相同保守基序相关联。基于这些结果，我们提出了一个耦合的 ATP 酶-腺苷酸激酶机制模型，涉及到典型和额外的核苷酸结合位点。我们将这些发现扩展到其他原核 ABC 外排泵，即 LmrA 和 TmrAB，表明偶联活性是 ABC 外排泵的一个普遍特征。
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