Porphyromonas gingivalis, an asaccharolytic member of the Bacteroidetes, is a keystone pathogen in human periodontitis that may also contribute to the development of other chronic inflammatory diseases. P. gingivalis utilizes protease-generated peptides derived from extracellular proteins for growth, but how these peptides enter the cell is not clear. Here, we identify RagAB as the outer-membrane importer for these peptides. X-ray crystal structures show that the transporter forms a dimeric RagA2B2 complex, with the RagB substrate-binding surface-anchored lipoprotein forming a closed lid on the RagA TonB-dependent transporter. Cryo-electron microscopy structures reveal the opening of the RagB lid and thus provide direct evidence for a 'pedal bin' mechanism of nutrient uptake. Together with mutagenesis, peptide-binding studies and RagAB peptidomics, our work identifies RagAB as a dynamic, selective outer-membrane oligopeptide-acquisition machine that is essential for the efficient utilization of proteinaceous nutrients by P. gingivalis.

中文翻译：

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RagAB 转运蛋白从牙龈卟啉单胞菌获取寡肽的结构和功能见解。


牙龈卟啉单胞菌是拟杆菌门的解糖成员，是人类牙周炎的关键病原体，也可能导致其他慢性炎症性疾病的发展。牙龈卟啉单胞菌利用源自细胞外蛋白的蛋白酶产生的肽进行生长，但这些肽如何进入细胞尚不清楚。在这里，我们将 RagAB 确定为这些肽的外膜输入者。 X射线晶体结构显示转运蛋白形成二聚体RagA2B2复合物，其中RagB底物结合表面锚定脂蛋白在RagA TonB依赖性转运蛋白上形成封闭盖。冷冻电子显微镜结构揭示了 RagB 盖子的开口，从而为营养吸收的“踏板箱”机制提供了直接证据。结合诱变、肽结合研究和 RagAB 肽组学，我们的工作将 RagAB 确定为一种动态、选择性外膜寡肽获取机器，对于牙龈卟啉单胞菌有效利用蛋白质营养物至关重要。