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Cryo-EM structures of pentameric autoinducer-2 exporter from Escherichia coli reveal its transport mechanism
The EMBO Journal ( IF 9.4 ) Pub Date : 2022-06-14 , DOI: 10.15252/embj.2021109990
Radhika Khera 1 , Ahmad R Mehdipour 2, 3 , Jani R Bolla 4, 5, 6 , Joerg Kahnt 7 , Sonja Welsch 8 , Ulrich Ermler 1 , Cornelia Muenke 1 , Carol V Robinson 4, 5 , Gerhard Hummer 2, 9 , Hao Xie 1 , Hartmut Michel 1
Affiliation  

Bacteria utilize small extracellular molecules to communicate in order to collectively coordinate their behaviors in response to the population density. Autoinducer-2 (AI-2), a universal molecule for both intra- and inter-species communication, is involved in the regulation of biofilm formation, virulence, motility, chemotaxis, and antibiotic resistance. While many studies have been devoted to understanding the biosynthesis and sensing of AI-2, very little information is available on its export. The protein TqsA from Escherichia coli, which belongs to the AI-2 exporter superfamily, has been shown to export AI-2. Here, we report the cryogenic electron microscopic structures of two AI-2 exporters (TqsA and YdiK) from E. coli at 3.35 Å and 2.80 Å resolutions, respectively. Our structures suggest that the AI-2 exporter exists as a homo-pentameric complex. In silico molecular docking and native mass spectrometry experiments were employed to demonstrate the interaction between AI-2 and TqsA, and the results highlight the functional importance of two helical hairpins in substrate binding. We propose that each monomer works as an independent functional unit utilizing an elevator-type transport mechanism.

中文翻译:

大肠杆菌五聚体自诱导物 2 出口蛋白的冷冻电镜结构揭示了其转运机制

细菌利用小的细胞外分子进行交流,以共同协调它们的行为以响应人口密度。Autoinducer-2 (AI-2) 是一种用于种内和种间交流的通用分子,参与调节生物膜形成、毒力、运动性、趋化性和抗生素耐药性。虽然许多研究致力于了解 AI-2 的生物合成和传感,但关于其出口的信息却很少。来自大肠杆菌的蛋白质 TqsA属于 AI-2 输出超家族,已被证明可以输出 AI-2。在这里,我们报告了来自大肠杆菌的两个 AI-2 出口商(TqsA 和 YdiK)的低温电子显微镜结构分辨率分别为 3.35 Å 和 2.80 Å。我们的结构表明 AI-2 输出物以同五聚体复合物的形式存在。采用计算机分子对接和原生质谱实验来证明 AI-2 和 TqsA 之间的相互作用,结果突出了两个螺旋发夹在底物结合中的功能重要性。我们建议每个单体作为一个独立的功能单元使用电梯式运输机制。
更新日期:2022-06-14
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