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标题：Molecular structure of an amyloid fibril formed by FUS low-complexity domain
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作者：Yunpeng Sun ; Shenqing Zhang ; Jiaojiao Hu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：1
页码：1-16
DOI：10.1016/j.isci.2021.103701
语种：English
出版社：Elsevier
摘要：SummaryFUS is a multifunctional nuclear protein which undergoes liquid–liquid phase separation in response to stress and DNA damage. Dysregulation of FUS dynamic phase separation leads to formation of pathological fibril closely associated with neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. In this study, we determined the cryo-EM structure of a cytotoxic fibril formed by the low-complexity (LC) domain of FUS at 2.9 Å resolution. The fibril structure exhibits a new and extensive serpentine fold consisting of three motifs incorporating together via a Tyr triad. FUS LC employs 91 residues to form an enlarged and stable fibril core via hydrophilic interaction and hydrogen bonds, which is distinct from most of previously determined fibrils commonly stabilized by hydrophobic interaction. Our work reveals the structural basis underlying formation of a cytotoxic and thermostable fibril of FUS LC and sheds light on understanding the liquid-to-solid phase transition of FUS in disease.Graphical abstractDisplay OmittedHighlights•Cryo-EM structure of an amyloid fibril formed by FUS low-complexity (LC) domain•FUS LC forms a novel enlarged and thermostable fibril core (FC) involving 91 residues•Hydrophilic interaction and hydrogen bonds are essential in FC formation of FUS LCBiochemistry; Biophysics; Structural biology