Chorell Erik, Andersson Emma, Evans Margery L, Jain Neha, Götheson Anna, Åden Jörgen, Chapman Matthew R, Almqvist Fredrik, Wittung-Stafshede Pernilla
Department of Chemistry, Umeå University, Umeå, Sweden.
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2015 Oct 14;10(10):e0140194. doi: 10.1371/journal.pone.0140194. eCollection 2015.
Amyloid formation is historically associated with cytotoxicity, but many organisms produce functional amyloid fibers (e.g., curli) as a normal part of cell biology. Two E. coli genes in the curli operon encode the chaperone-like proteins CsgC and CsgE that both can reduce in vitro amyloid formation by CsgA. CsgC was also found to arrest amyloid formation of the human amyloidogenic protein α-synuclein, which is involved in Parkinson's disease. Here, we report that the inhibitory effects of CsgC arise due to transient interactions that promote the formation of spherical α-synuclein oligomers. We find that CsgE also modulates α-synuclein amyloid formation through transient contacts but, in contrast to CsgC, CsgE accelerates α-synuclein amyloid formation. Our results demonstrate the significance of transient protein interactions in amyloid regulation and emphasize that the same protein may inhibit one type of amyloid while accelerating another.
淀粉样蛋白的形成在历史上与细胞毒性相关，但许多生物体将功能性淀粉样纤维（如卷曲菌毛）作为细胞生物学的正常组成部分产生。卷曲菌毛操纵子中的两个大肠杆菌基因编码伴侣样蛋白CsgC和CsgE，它们都可以在体外减少CsgA的淀粉样蛋白形成。还发现CsgC能阻止参与帕金森病的人类淀粉样蛋白生成蛋白α-突触核蛋白的淀粉样蛋白形成。在这里，我们报告CsgC的抑制作用是由于促进球形α-突触核蛋白寡聚体形成的瞬时相互作用而产生的。我们发现CsgE也通过瞬时接触调节α-突触核蛋白的淀粉样蛋白形成，但与CsgC相反，CsgE加速α-突触核蛋白的淀粉样蛋白形成。我们的结果证明了瞬时蛋白质相互作用在淀粉样蛋白调节中的重要性，并强调同一蛋白质可能抑制一种类型的淀粉样蛋白，同时加速另一种类型的淀粉样蛋白。
