1月5日,，國際著名雜志Nature在線刊登了國外研究人員的最新研究成果“Antiparallel EmrE exports drugs by exchanging between asymmetric structures。”,，文章中,，作者揭示了大腸桿菌小型運(yùn)輸因子EmrE的結(jié)構(gòu)特點(diǎn),。
EmrE是大腸桿菌中能夠抵抗多種藥物的小型運(yùn)輸因子,，能夠輸出包括很多藥物在內(nèi)的一大類多環(huán)芳烴陽離子基質(zhì),。EmrE同型二聚體的總體結(jié)構(gòu)和拓?fù)湟恢笔且粋€相當(dāng)有爭議的話題。這篇論文所報(bào)告的核磁共振和單分子FRET實(shí)驗(yàn)表明,，這種膜蛋白的單體亞單元是以“反平行”走向排列的,。這一結(jié)果說明存在一個二聚結(jié)構(gòu),，該結(jié)構(gòu)在某一個給定的時(shí)間只向膜的一邊開放,。（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.
