Localized and efficient curli nucleation requires the chaperone-like amyloid assembly protein CsgF
Localized and efficient curli nucleation requires the chaperone-like amyloid assembly protein CsgF
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DOI：
10.1073/pnas.0812143106
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发表时间：
2009-01-20
影响因子：
11.1
通讯作者：
Hultgren, Scott J.
中科院分区：
文献类型：
--
作者：
Nenninger, Ashley A.;Robinson, Lloyd S.;Hultgren, Scott J.
阐明淀粉样蛋白形成的早期事件是理解淀粉样蛋白疾病的病理学和开发治疗方法的关键。这些早期事件的关键信息是淀粉样蛋白组装蛋白，它促进了从单体到淀粉样蛋白纤维的转变。Curli是一种功能性淀粉样蛋白，其体内聚合需要专用的成核蛋白CsgB和组装蛋白CsgF。在这里，我们证明，没有CsgF，curli亚基从细胞释放到介质中，聚合效率低下，导致更少的和错误定位的curli纤维。CsgF被分泌到细胞表面，在那里它介导CsgB成核剂的细胞缔合和蛋白酶抗性，表明CsgF是CsgB的特异性定位和/或伴侣作用所需的，以获得完整的成核剂活性。因此，CsgF对于实现纤维亚基局部和有效成核成功能性细胞相关淀粉样蛋白至关重要。
Elucidation of the early events in amyloidogenesis is key to understanding the pathology of, and developing therapies for, amyloid diseases. Critical informants about these early events are amyloid assembly proteins that facilitate the transition from monomer to amyloid fiber. Curli are a functional amyloid whose in vivo polymerization requires a dedicated nucleator protein, CsgB, and an assembly protein, CsgF. Here we demonstrate that without CsgF, curli subunits are released from the cell into the media and are inefficiently polymerized, resulting in fewer and mislocalized curli fibers. CsgF is secreted to the cell surface, where it mediates the cell-association and protease-resistance of the CsgB nucleator, suggesting that CsgF is required for specific localization and/or chaperoning of CsgB for full nucleator activity. CsgF is thus critical to achieve localized and efficient nucleation of fiber subunits into functional, cell-associated amyloid.