1月5日,国际著名杂志Nature在线刊登了国外研究人员的最新研究成果“Antiparallel EmrE exports drugs by exchanging between asymmetric structures。”,文章中,作者揭示了大肠杆菌小型运输因子EmrE的结构特点。
EmrE是大肠杆菌中能够抵抗多种药物的小型运输因子,能够输出包括很多药物在内的一大类多环芳烃阳离子基质。EmrE同型二聚体的总体结构和拓扑一直是一个相当有争议的话题。这篇论文所报告的核磁共振和单分子FRET实验表明,这种膜蛋白的单体亚单元是以“反平行”走向排列的。这一结果说明存在一个二聚结构,该结构在某一个给定的时间只向膜的一边开放。(生物谷Bioon.com)
doi:10.1038/nature10703
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Antiparallel EmrE exports drugs by exchanging between asymmetric structures
Emma A. Morrison, Gregory T. DeKoster, Supratik Dutta, Reza Vafabakhsh, Michael W. Clarkson, Arjun Bahl, Dorothee Kern, Taekjip Ha & Katherine A. Henzler-Wildman
Small multidrug resistance transporters provide an ideal system to study the minimal requirements for active transport. EmrE is one such transporter in Escherichia coli. It exports a broad class of polyaromatic cation substrates, thus conferring resistance to drug compounds matching this chemical description. However, a great deal of controversy has surrounded the topology of the EmrE homodimer. Here we show that asymmetric antiparallel EmrE exchanges between inward- and outward-facing states that are identical except that they have opposite orientation in the membrane. We quantitatively measure the global conformational exchange between these two states for substrate-bound EmrE in bicelles using solution NMR dynamics experiments. Förster resonance energy transfer reveals that the monomers within each dimer are antiparallel, and paramagnetic relaxation enhancement NMR experiments demonstrate differential water accessibility of the two monomers within each dimer. Our experiments reveal a ‘dynamic symmetry’ that reconciles the asymmetric EmrE structure with the functional symmetry of residues in the active site.