期刊
MOLECULAR CELL
卷 60, 期 2, 页码 231-241出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.09.006
关键词
-
资金
- Rhode Island Foundation [20133966]
- Richard B. Salomon Faculty Research Award from Brown University
- Center for Biomedical Research Excellence in Skeletal Health and Repair from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM104937]
- Rhode Island IDeA Network for Excellence in Biomedical research, Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
- National Science Foundation EPSCoR [1004057]
- National Institutes of Health [S10RR020923]
- Rhode Island Science and Technology Advisory Council
- ivision of Biology and Medicine, Brown University
- NIH (NIGMS) [P30GM103410]
- NIH (NCRR) [P30RR031153, P20RR018728, S10RR02763]
- National Science Foundation (EPSCoR) [0554548]
- Lifespan Rhode Island Hospital
- Division of Biology and Medicine, Brown University
- Office of Integrative Activities
- Office Of The Director [1004057] Funding Source: National Science Foundation
Phase-separated states of proteins underlie ribonucleoprotein (RNP) granules and nuclear RNA-binding protein assemblies that may nucleate protein inclusions associated with neurodegenerative diseases. We report that the N-terminal low-complexity domain of the RNA-binding protein Fused in Sarcoma (FUS LC) is structurally disordered and forms a liquid-like phase-separated state resembling RNP granules. This state directly binds the C-terminal domain of RNA polymerase II. Phase-separated FUS lacks static structures as probed by fluorescence microscopy, indicating they are distinct from both protein inclusions and hydrogels. We use solution nuclear magnetic resonance spectroscopy to directly probe the dynamic architecture within FUS liquid phase-separated assemblies. Importantly, we find that FUS LC retains disordered secondary structure even in the liquid phase-separated state. Therefore, we propose that disordered protein granules, even those made of aggregation-prone prion-like domains, are dynamic and disordered molecular assemblies with transiently formed protein-protein contacts.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据