Structure of the nonameric bacterial amyloid secretion channel
Structure of the nonameric bacterial amyloid secretion channel
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DOI：
10.1073/pnas.1411942111
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发表时间：
2014-12-16
影响因子：
11.1
通讯作者：
Huang, Yihua
中科院分区：
文献类型：
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作者：
Cao, Baohua;Zhao, Yan;Huang, Yihua
不同菌株的细菌能够产生一种独特的功能淀粉样蛋白，称为卷曲，它对生物膜的形成、宿主细胞的黏附和惰性表面的定植至关重要。卷曲是通过VIII型细菌分泌系统分泌的，它们与淀粉样纤维具有共同的生化和结构特征，后者与人类的有害疾病有关。在这里，我们报道了大肠杆菌CsgG的晶体结构，它是分泌系统的重要脂蛋白成分，在细菌外膜上形成了运输Curli亚基的分泌通道。CsgG形成一个冠状对称的非聚体通道，通过一个36链的β-桶横跨外膜，每个亚基贡献四条β-链。这个非聚集体复合体包含一个中央通道，中间有一个孔。孔的小孔直径类似于12埃，内衬三个由Tyr-66、ASN-70或Phe-71组成的堆叠的九残基环。我们基于结构的功能研究表明，Tyr-66和Phe-71残基是选择性分泌Curli亚基的守门人。据我们所知，我们的研究详细描述了VIII型细菌分泌物机械的第一个核心结构。重要的是，我们的结构分析表明，卷曲亚基是通过CsgG以未折叠的形式通过细菌外膜分泌的。
Various strains of bacteria are able to produce a unique class of functional amyloids termed curli, which are critical for biofilm formation, host cell adhesion, and colonization of inert surfaces. Curli are secreted via the type VIII bacterial secretion system, and they share biochemical and structural characteristics with amyloid fibers that have been implicated in deleterious disease in humans. Here, we report the crystal structure of Escherichia coli CsgG, which is an essential lipoprotein component of the type VIII secretion system and which forms a secretion channel in the bacterial outer membrane for transporting curli subunits. CsgG forms a crown-shaped, symmetric nonameric channel that spans the outer membrane via a 36-strand beta-barrel, with each subunit contributing four beta-strands. This nonameric complex contains a central channel with a pore located at the middle. The eyelet of the pore is similar to 12 angstrom in diameter and is lined with three stacked nine-residue rings consisting of Tyr-66, Asn-70, or Phe-71. Our structure-based functional studies suggest that Tyr-66 and Phe-71 residues function as gatekeepers for the selective secretion of curli subunits. Our study describes in detail, to our knowledge, the first core structure of the type VIII bacterial secretion machinery. Importantly, our structural analysis suggests that the curli subunits are secreted via CsgG across the bacterial outer membrane in an unfolded form.