Curli是由细菌Curli分泌系统分泌和组装的功能性淀粉样蛋白，作为细菌生物膜重要的结构功能部件，它介导细菌与宿主细胞间的粘附和侵染，导致细菌抗生素抵抗并逃逸宿主的免疫清除。该分泌系统中的分子伴侣CsgE和CsgF在Curli组分CsgA和CsgB的分泌，折叠以及细胞膜定位与组装中发挥了至关重要的作用，而其调控分子机制还不明确。本项目采用一体化结构生物学方案，解析Curli分泌过程中CsgE与外膜孔道蛋白CsgG相互作用，膜定位过程中CsgF与CsgB相互作用复合物晶体结构，同时揭示CsgE在周质区识别并抑制CsgA折叠为成熟富β折叠结构的分子机制，在此基础上构建基因敲除和关键氨基酸位点突变的菌株明确分子伴侣在生理水平的调控机制。系统性的阐明分子伴侣CsgE和CsgF在Curli分泌和组装中的原子水平晶体结构及生理水平调控分子机制，并为以抑制生物膜形成为基础的细菌抗感染治疗提供新的策略。

Curli is functional amyloid with its secretion and assembly modulated by bacterial curli secretion system. As the major structure component of bacterial biofilm, Curli mediates the adhesion and invasion between the bacteria and host cells, results in the antibiotic resistance and escapes from the host immune elimination. The Chaperone CsgE and CsgF plays a critical role in the secretion, folding, cell membrane anchoring and assembly of curli subunits CsgA and CsgB, however the molecular mechanism of those procedures are still elusive. We will apply the integrative structural biology approach, firstly we aim to solve the crystal structures of the CsgE-CsgG complex of the secretion and CsgF-CsgB complex of the cell membrane anchoring, further the molecular mechanism of how CsgE prevent the CsgA folding into the β sheet rich structure will be revealed, what is especially noteworthy, the CsgE and CsgF knockout strain and the mutants of the key regulation amino acids will be carried out to investigate the physiological roles of the CsgE and CsgF. The atomic resolution crystal structure information and the physiological study will provide systematic view of the molecular mechanism of the Chaperone CsgE and CsgF in the Curli secretion and assembly. The study will enlighten the molecular mechanism study of the chaperone role in the human neuron toxic amyloid folding and guide to develop new strategies based on biofilm formation inhibition for the bacterial anti-infection therapy.