Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly

doi:10.1038/s41467-019-09902-7

	Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly
	Gui, Xinrui 1,2; Luo, Feng 1,2; Li, Yichen 3; Zhou, Heng 4; Qin, Zhenheng5 ; Liu, Zhenying 1,2; Gu, Jinge 1,2; Xie, Muyun 6; Zhao, Kun 1,2; Dai, Bin 1; Shin, Woo Shik 7,8; He, Jianhua 6; He, Lin 3; Jiang, Lin 7,8; Zhao, Minglei 9; Sun, Bo5 ; Li, Xueming 4; Liu, Cong 1,2; Li, Dan 3
	2019-05
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	10
发表状态	已发表
DOI	10.1038/s41467-019-09902-7
摘要	Subcellular membrane-less organelles consist of proteins with low complexity domains. Many of them, such as hnRNPA1, can assemble into both a polydisperse liquid phase and an ordered solid phase of amyloid fibril. The former mirrors biological granule assembly, while the latter is usually associated with neurodegenerative disease. Here, we observe a reversible amyloid formation of hnRNPA1 that synchronizes with liquid-liquid phase separation, regulates the fluidity and mobility of the liquid-like droplets, and facilitates the recruitment of hnRNPA1 into stress granules. We identify the reversible amyloid-forming cores of hnRNPA1 (named hnRACs). The atomic structures of hnRACs reveal a distinct feature of stacking Asp residues, which contributes to fibril reversibility and explains the irreversible pathological fibril formation caused by the Asp mutations identified in familial ALS. Our work characterizes the structural diversity and heterogeneity of reversible amyloid fibrils and illuminates the biological function of reversible amyloid formation in protein phase separation.
收录类别	SCI ; SCIE
语种	英语
资助项目	Innovation Program of Shanghai Municipal Education Commission[2019-01-07-00-02-E00037]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000466337500007
出版者	NATURE PUBLISHING GROUP
WOS关键词	RNA-BINDING PROTEINS ; CELL-FREE FORMATION ; PRION-LIKE DOMAINS ; PHASE-SEPARATION ; ATOMIC STRUCTURES ; BETA-SHEETS ; STATE ; FUS ; TRANSITION ; MUTATIONS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/37515
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_孙博组
通讯作者	Liu, Cong; Li, Dan
作者单位	1.Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai, Peoples R China 4.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Appl Phys, 239 Zhang Heng Rd, Shanghai 201203, Peoples R China 7.Univ Calif Los Angeles, Mol Biol Inst, Dept Neurol, Los Angeles, CA 90095 USA 8.Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA 9.Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
推荐引用方式 GB/T 7714	Gui, Xinrui,Luo, Feng,Li, Yichen,et al. Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly[J]. NATURE COMMUNICATIONS,2019,10.
APA	Gui, Xinrui.,Luo, Feng.,Li, Yichen.,Zhou, Heng.,Qin, Zhenheng.,...&Li, Dan.(2019).Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly.NATURE COMMUNICATIONS,10.
MLA	Gui, Xinrui,et al."Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly".NATURE COMMUNICATIONS 10(2019).