Department of Biochemistry, University of Oxford, Oxford, UK.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Nature. 2018 Dec;564(7734):77-82. doi: 10.1038/s41586-018-0693-y. Epub 2018 Nov 7.
The type 9 secretion system (T9SS) is the protein export pathway of bacteria of the Gram-negative Fibrobacteres-Chlorobi-Bacteroidetes superphylum and is an essential determinant of pathogenicity in severe periodontal disease. The central element of the T9SS is a so-far uncharacterized protein-conducting translocon located in the bacterial outer membrane. Here, using cryo-electron microscopy, we provide structural evidence that the translocon is the T9SS protein SprA. SprA forms an extremely large (36-strand) single polypeptide transmembrane β-barrel. The barrel pore is capped on the extracellular end, but has a lateral opening to the external membrane surface. Structures of SprA bound to different components of the T9SS show that partner proteins control access to the lateral opening and to the periplasmic end of the pore. Our results identify a protein transporter with a distinctive architecture that uses an alternating access mechanism in which the two ends of the protein-conducting channel are open at different times.
9 型分泌系统（T9SS）是革兰氏阴性纤维杆菌-绿弯菌-拟杆菌超门细菌的蛋白质外排途径，是严重牙周病致病的重要决定因素。T9SS 的核心元件是一种尚未被描述的位于细菌外膜中的蛋白导运转位器。在这里，我们使用低温电子显微镜提供了结构证据，证明转位器是 T9SS 蛋白 SprA。SprA 形成一个非常大的（36 股）单多肽跨膜β桶。桶孔在细胞外端被封闭，但在外部膜表面有一个侧向开口。与 T9SS 的不同成分结合的 SprA 结构表明，伴侣蛋白控制着侧向开口和孔的周质端的进入。我们的结果鉴定了一种具有独特结构的蛋白转运体，它使用交替访问机制，其中蛋白导运通道的两端在不同时间打开。
