报告题目:The structural basis of reversible amyloids involved in protein phase separation and neurodegenerative diseases

报告人:  刘聪博士

中国科学院生物与化学交叉研究中心，研究员

时间：    2019年1月7日（周一），上午：10:30-11:30

地点：西区生物楼429会议室

主办单位：中国科学院脑功能与脑疾病重点实验室

中国科学技术大学生命科学学院

合肥微尺度物质科学国家研究中心集成影像中心

报告简介：

Pathological amyloid fibrils are characteristic of highly thermostable cross-β structure1. However, the stable cross-β architecture cannot explain the reversible amyloid fibrils formed by RNA-binding proteins such as hnRNPA1 and FUS that is involved in the dynamic assembly of stress granules. Here we found that the reversible amyloid cores (RACs) of FUS and hnRNPA1 that can form reversible amyloid fibrils in the liquid-like droplet under the regulation of temperature and phosphorylation. We determined the atomic structures of the RACs in fibrillar forms by micro-electron diffraction. Combined with biochemical and cellular experiments, we reveal the structural basis of reversible amyloid formation and its role in liquid-liquid phase separation, and explains how ALS disease-associated mutation abolishes reversibility of RACs which results in abnormal aggregation observed in the brain of ALS patients. Our study sheds light on understanding not only the dynamic amyloid formation in RNA granules but also how the dysregulation of reversible amyloid leads to diseases.