Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Nature. 2023 Jun;618(7965):583-589. doi: 10.1038/s41586-023-06146-w. Epub 2023 Jun 7.
Bacteroidetes are abundant members of the human microbiota, utilizing a myriad of diet- and host-derived glycans in the distal gut. Glycan uptake across the bacterial outer membrane of these bacteria is mediated by SusCD protein complexes, comprising a membrane-embedded barrel and a lipoprotein lid, which is thought to open and close to facilitate substrate binding and transport. However, surface-exposed glycan-binding proteins and glycoside hydrolases also play critical roles in the capture, processing and transport of large glycan chains. The interactions between these components in the outer membrane are poorly understood, despite being crucial for nutrient acquisition by our colonic microbiota. Here we show that for both the levan and dextran utilization systems of Bacteroides thetaiotaomicron, the additional outer membrane components assemble on the core SusCD transporter, forming stable glycan-utilizing machines that we term utilisomes. Single-particle cryogenic electron microscopy structures in the absence and presence of substrate reveal concerted conformational changes that demonstrate the mechanism of substrate capture, and rationalize the role of each component in the utilisome.
拟杆菌门是人类微生物群的丰富成员，在远端肠道中利用各种饮食和宿主来源的聚糖。这些细菌通过 SusCD 蛋白复合物介导细菌外膜上的聚糖摄取，该复合物由一个膜嵌入桶和一个脂蛋白盖组成，据认为它打开和关闭以促进底物结合和运输。然而，表面暴露的聚糖结合蛋白和糖苷水解酶在捕获、加工和运输大聚糖链方面也起着关键作用。尽管这些成分在外膜中的相互作用对我们结肠微生物群获取营养物质至关重要，但目前对其了解甚少。在这里，我们表明，对于双歧杆菌的左旋糖和葡聚糖利用系统，额外的外膜成分组装在核心 SusCD 转运体上，形成稳定的聚糖利用机器，我们称之为利用体。在无底物和有底物的情况下进行的单颗粒低温电子显微镜结构揭示了协同的构象变化，证明了底物捕获的机制，并合理说明了利用体中每个成分的作用。
