Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation.
Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation.
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CsgE 的溶液 NMR 结构：对功能性淀粉样蛋白形成重要的分子伴侣和调节蛋白的结构见解。
DOI：
10.1073/pnas.1607222113
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发表时间：
2016
影响因子：
11.1
通讯作者：
Frieden,Carl
中科院分区：
文献类型：
--
作者：
Shu,Qin;Krezel,AndrzejM;Cusumano,ZacharyT;Pinkner,JeromeS;Klein,Roger;Hultgren,ScottJ;Frieden,Carl
Curli主要由主要结构亚基CsgA组成，是在大肠杆菌和许多其他肠道细菌表面产生的功能性淀粉样蛋白，参与细胞定植和生物膜的形成。CsgE是一种在卷曲生物发生中起重要作用的外质辅助蛋白。CsgE可以结合CsgA和非美国孔蛋白CsgG。CsgG-CsgE复合物是卷毛分泌通道，对体内卷毛原纤维的形成至关重要。为了更好的理解这个角色的CsgE curli形成,我们已经确定的解决方案NMR结构双突变体的CsgE (W48A / F79A)这似乎是类似于野生型(WT)蛋白在总体结构和功能但不形成混合寡聚物在NMR浓度类似于WT。这种突变的well-converged结构核心支架组成的一层两个α螺旋和一层三股反平行的β片与灵活的N和C末端。CsgE的结构与CsgG-CsgE配合物的低温电镜密度图吻合良好。我们强调了静电势面在CsgE结构中的显著特征，并提出了CsgG-CsgE复合物的组装模型。我们提出了CsgE和CsgA相互作用的结构机制。了解卷曲形成可以为开发生物膜相关感染的治疗方法和治疗剂提供必要的信息，并可能有助于预防和治疗淀粉样蛋白疾病。由于其在卷曲蛋白形成中的独特作用，CsgE可以为淀粉样蛋白的形成调节建立一个范例。
Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface ofEscherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. CsgE binds to both CsgA and the nonameric pore protein CsgG. The CsgG–CsgE complex is the curli secretion channel and is essential for the formation of the curli fibril in vivo. To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. The well-converged structure of this mutant has a core scaffold composed of a layer of two α-helices and a layer of three-stranded antiparallel β-sheet with flexible N and C termini. The structure of CsgE fits well into the cryoelectron microscopy density map of the CsgG–CsgE complex. We highlight a striking feature of the electrostatic potential surface in CsgE structure and present an assembly model of the CsgG–CsgE complex. We suggest a structural mechanism of the interaction between CsgE and CsgA. Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. CsgE could establish a paradigm for the regulation of amyloidogenesis because of its unique role in curli formation.