Conformational snapshots of the bacitracin sensing and resistance transporter BceAB.
Conformational snapshots of the bacitracin sensing and resistance transporter BceAB.
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DOI：
10.1073/pnas.2123268119
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发表时间：
2022-04-05
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
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许多革兰氏阳性菌已经进化出一种优雅的解决方案来感知和抵抗抑制细胞壁合成的抗菌肽。这些生物表达一种不寻常的“Bce型”三磷酸腺苷结合盒（ABC）转运蛋白，该转运蛋白识别参与细胞壁生物合成的抗菌肽和脂质之间形成的复合物。在这项工作中，我们提供了第一个结构快照的BCE型ABC转运蛋白被困在不同的构象状态。我们的结构和相关的生物化学数据提供了关键的见解，这些不寻常的ABC转运蛋白用于感测和抵抗抗菌肽的新的目标保护机制。本文所述的研究为开始发展对抗菌肽与大多数革兰氏阳性生物体中发现的保守抗性机制之间的多种相互作用的全面分子理解奠定了基础。抗菌肽是多种多样的分子，包括强大的药物，如杆菌肽和万古霉素，以及有效的细菌信号分子。几种抗菌肽通过与脂质II循环中间体结合并抑制肽聚糖的合成而引起革兰氏阳性菌的细胞死亡。许多革兰氏阳性微生物已经进化出一种优雅的机制来感知和抵抗这种抗菌肽。在这些生物体中，“Bce型”三磷酸腺苷结合盒（ABC）转运蛋白与双组分系统形成蛋白复合物，并且这些组分一起感知存在于细胞表面的抗微生物肽并提供对所述抗微生物肽的抗性。Bce型转运蛋白的构象转换被认为是通过一种新的通量感应机制激活相关双组分系统的刺激。在这项工作中，我们确定了洗涤剂溶解的结构的BCE型ABC转运BceAB从枯草芽孢杆菌在两个不同的构象状态，使用冷冻电子显微镜。结合质谱和酶数据，我们的结构揭示了Bce型转运蛋白家族的整体结构，揭示了脂质II循环中间体的专门脂质结合口袋，并揭示了通过相关的双组分系统启动信号传导的构象变化。
Many gram-positive organisms have evolved an elegant solution to sense and resist antimicrobial peptides that inhibit cell-wall synthesis. These organisms express an unusual “Bce-type” adenosine triphosphate–binding cassette (ABC) transporter that recognizes complexes formed between antimicrobial peptides and lipids involved in cell-wall biosynthesis. In this work, we provide the first structural snapshots of a Bce-type ABC transporter trapped in different conformational states. Our structures and associated biochemical data provide key insights into the novel target protection mechanism that these unusual ABC transporters use to sense and resist antimicrobial peptides. The studies described herein set the stage to begin developing a comprehensive molecular understanding of the diverse interactions between antimicrobial peptides and conserved resistance machinery found across most gram-positive organisms. Antimicrobial peptides are diverse molecules that include powerful medications such as bacitracin and vancomycin, as well as potent bacterial signaling molecules. Several antimicrobial peptides elicit cell death in gram-positive species by binding to lipid II cycle intermediates and inhibiting the synthesis of peptidoglycan. Many gram-positive organisms have evolved an elegant mechanism to sense and resist such antimicrobial peptides. In these organisms, a “Bce-type” adenosine triphosphate–binding cassette (ABC) transporter forms a protein complex with a two-component system, and together these components sense and provide resistance to antimicrobial peptides present at the cell surface. Conformational switching of Bce-type transporters is proposed to be the stimulus that activates the associated two-component system through a novel flux-sensing mechanism. In this work, we determined the detergent-solubilized structure of the Bce-type ABC transporter BceAB from Bacillus subtilis in two distinct conformational states using cryo–electron microscopy. Together with mass spectrometry and enzymatic data, our structures reveal the overall architecture of the Bce-type transporter family, uncover a specialized lipid-binding pocket for lipid II cycle intermediates, and reveal the conformational changes that are proposed to initiate signaling through the associated two-component system.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.6
作者：
Gebhard, Susanne;Mascher, Thorsten
通讯作者：
Mascher, Thorsten
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.
影响因子：
4.8
作者：
Breazeale, SD;Ribeiro, AA;Raetz, CRH
通讯作者：
Raetz, CRH
影响因子：
4.9
作者：
Kobras, Carolin M.;Piepenbreier, Hannah;Gebhard, Susanne
通讯作者：
Gebhard, Susanne