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 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.

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

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

2021 ◽  
Author(s):  
Li-Qiang Wang ◽  
Kun Zhao ◽  
Han-Ye Yuan ◽  
Xiang-Ning Li ◽  
Hai-Bin Dang ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Prion Diseases ◽  
Conformational Stability ◽  
Salt Bridges ◽  
Wild Type ◽  
Left Handed ◽  
Prion Strains ◽  
Fibril Structure ◽  
Clinical Syndromes ◽  
Jakob Disease

Prion diseases are caused by the conformational conversion of prion protein (PrP) from its cellular form (PrPC) into a protease-resistant, aggregated form (PrPSc). 42 different familial mutations were identified in human PrP, which lead to genetic prion diseases with distinct clinical syndromes. Here we report cryo-EM structure of an amyloid fibril formed by full-length human PrP with E196K mutation, a familial Creutzfeldt-Jakob disease-related mutation. This mutation disrupts key interactions in wild-type PrP fibril and results in a rearrangement of the overall structure, forming an amyloid fibril with a conformation distinct from wild-type PrP fibril. The E196K fibril consists of two protofibrils intertwined into a left-handed helix. Each subunit forms five β-strands stabilized by a disulfide bond and an unusual hydrophilic cavity. Two pairs of amino acids (Lys194 and Glu207; Lys196 and Glu200) from opposing subunits form four salt bridges to stabilize the zigzag interface of the two protofibrils. Furthermore, the E196K fibril exhibits a significantly lower conformational stability and protease resistance activity than the wild-type fibril. Our results provide direct structural evidences of the diverse mammalian prion strains and fibril polymorphism of PrP, and highlight the importance of familial mutations in determining the different prion strains.

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