Pathogenic siderophore ABC importer YbtPQ adopts a surprising fold of exporter.
Pathogenic siderophore ABC importer YbtPQ adopts a surprising fold of exporter.
复制标题
致病性铁载体 ABC 输入蛋白 YbtPQ 采用了令人惊讶的输出蛋白折叠。
DOI：
10.1126/sciadv.aay7997
复制
发表时间：
2020
期刊：
影响因子：
13.6
通讯作者：
Zheng,Hongjin
中科院分区：
文献类型：
--
作者：
Wang,Zhiming;Hu,Wenxin;Zheng,Hongjin
为了获得必需的金属离子，人类病原体首先分泌毒力相关的铁载体，然后通过ATP结合盒（ABC）输入子亚家族重新摄取金属螯合的铁载体，然而，其分子机制迄今为止完全未知。在这里，我们通过冷冻电子显微镜确定了来自尿路致病性大肠杆菌 (UPEC) 的耶尔森菌素输入蛋白 YbtPQ 复合物在 apo 和底物结合状态下的向内开放构象的多种结构。令人惊讶的是，YbtPQ 没有采用任何已知的 ABC 导入器折叠，而是采用 IV 型 ABC 导出器折叠。据我们所知，这是首次报道ABC进口商的出口商倒闭。此外，我们还观察到 YbtPQ 的两个独特特征：YbtP 中的跨膜螺旋在底物释放时解旋，以及紧密相关的核苷酸结合结构域而没有核苷酸结合。总而言之，我们的研究表明，铁载体 ABC 输入蛋白应被归类为一个单独的亚科，并且与其他亚科相比具有独特的运输机制。
To obtain essential metal ions, human pathogens secrete virulence-associated siderophores at first and then retake the metal-chelated siderophores through a subfamily of ATP-binding cassette (ABC) importer, however, the molecular mechanisms are completely unknown till now. Here, we have determined multiple structures of yersiniabactin importer YbtPQ complex from uropathogenic Escherichia coli (UPEC) at inward-open conformation in both apo and substrate-bound states by cryo electron microscopy. Surprisingly, YbtPQ does not adopt any known fold of ABC importers, but adopt the fold of Type IV ABC exporters. To our knowledge, it is the first time an exporter fold of ABC importer has been reported. In addition, we have observed two unique features in YbtPQ: unwinding of a transmembrane helix in YbtP upon substrate release, as well as tightly associated nucleotide-binding domains without nucleotide bound. Altogether, our study suggests that siderophore ABC importers should be classified as a separate subfamily and have a distinct transport mechanism comparing to others.