scholarly journals Genetic prion disease–related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM

2021 ◽  
Vol 7 (37) ◽  
Author(s):  
Li-Qiang Wang ◽  
Kun Zhao ◽  
Han-Ye Yuan ◽  
Xiang-Ning Li ◽  
Hai-Bin Dang ◽  
...  
Keyword(s):  
Prion Disease ◽  
Amyloid Fibril ◽  
Fibril Structure

scholarly journals The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure

2020 ◽  
Author(s):  
Yunpeng Sun ◽  
Kun Zhao ◽  
Wencheng Xia ◽  
Jinge Gu ◽  
Yeyang Ma ◽  
...  
Keyword(s):  
Phase Separation ◽  
Nuclear Localization ◽  
Amyloid Fibril ◽  
Low Complexity ◽  
Nuclear Localization Sequence ◽  
Amyloid Aggregation ◽  
Dynamic Phase ◽  
Fibril Structure ◽  
Cytoplasmic Transport ◽  
Localization Sequence

AbstractHuman heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminate structural understandings on the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.

2P022 Amyloid fibril structure proposed from IR-microscope linear dichroism

2004 ◽  
Vol 44 (supplement) ◽  
pp. S115
Author(s):  
H. Hiramatsu ◽  
Y. Goto ◽  
H. Naiki ◽  
T. Kitagawa
Keyword(s):  
Amyloid Fibril ◽  
Linear Dichroism ◽  
Fibril Structure

scholarly journals Scanning tunnelling microscopy studies of β-amyloid fibril structure and assembly

FEBS Letters ◽  
1995 ◽  
Vol 371 (1) ◽  
pp. 25-28 ◽  
Author(s):  
A.P. Shivji ◽  
F. Brown ◽  
M.C. Davies ◽  
K.H. Jennings ◽  
C.J. Roberts ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Scanning Tunnelling Microscopy ◽  
Fibril Structure ◽  
Scanning Tunnelling ◽  
Tunnelling Microscopy ◽  
Β Amyloid

scholarly journals The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunpeng Sun ◽  
Kun Zhao ◽  
Wencheng Xia ◽  
Guoqin Feng ◽  
Jinge Gu ◽  
...  
Keyword(s):  
Phase Separation ◽  
Nuclear Localization ◽  
Amyloid Fibril ◽  
Low Complexity ◽  
Nuclear Localization Sequence ◽  
Amyloid Aggregation ◽  
Dynamic Phase ◽  
Fibril Structure ◽  
Cytoplasmic Transport ◽  
Localization Sequence

AbstractHuman heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminates structural understandings of the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.

scholarly journals Ideas of Order for Amyloid Fibril Structure

Structure ◽  
2002 ◽  
Vol 10 (8) ◽  
pp. 1031-1036 ◽  
Author(s):  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Fibril Structure

scholarly journals Higher Order Amyloid Fibril Structure by MAS NMR and DNP Spectroscopy

2013 ◽  
Vol 135 (51) ◽  
pp. 19237-19247 ◽  
Author(s):  
Galia T. Debelouchina ◽  
Marvin J. Bayro ◽  
Anthony W. Fitzpatrick ◽  
Vladimir Ladizhansky ◽  
Michael T. Colvin ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Higher Order ◽  
Mas Nmr ◽  
Fibril Structure

FT-IR approaches on amyloid fibril structure

2005 ◽  
Vol 1753 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Hirotsugu Hiramatsu ◽  
Teizo Kitagawa
Keyword(s):  
Amyloid Fibril ◽  
Fibril Structure ◽  
Ft Ir
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