scholarly journals Amyloid fibril structure of α-synuclein determined by cryo-electron microscopy

Cell Research ◽  
2018 ◽  
Vol 28 (9) ◽  
pp. 897-903 ◽  
Author(s):  
Yaowang Li ◽  
Chunyu Zhao ◽  
Feng Luo ◽  
Zhenying Liu ◽  
Xinrui Gui ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Amyloid Fibril ◽  
Cryo Electron Microscopy ◽  
Fibril Structure

scholarly journals Fibril structure of amyloid-β(1–42) by cryo–electron microscopy

Science ◽  
2017 ◽  
Vol 358 (6359) ◽  
pp. 116-119 ◽  
Author(s):  
Lothar Gremer ◽  
Daniel Schölzel ◽  
Carla Schenk ◽  
Elke Reinartz ◽  
Jörg Labahn ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Dimer Interface ◽  
Cryo Electron Microscopy ◽  
Fibril Structure ◽  
Β Protein ◽  
Density Map ◽  
Main Component

Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer’s disease patients. We present the structure of an Aβ(1–42) fibril composed of two intertwined protofilaments determined by cryo–electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall “LS”-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed “groove” and “ridge,” leading to different binding pathways on both fibril ends, which has implications for fibril growth.

scholarly journals Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing

1999 ◽  
Vol 18 (4) ◽  
pp. 815-821 ◽  
Author(s):  
José L. Jiménez ◽  
J.Iñaki Guijarro ◽  
Elena Orlova ◽  
Jesús Zurdo ◽  
Christopher M. Dobson ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Amyloid Fibril ◽  
Molecular Packing ◽  
Cryo Electron Microscopy

scholarly journals Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthias Schmidt ◽  
Sebastian Wiese ◽  
Volkan Adak ◽  
Jonas Engler ◽  
Shubhangi Agarwal ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
The Body ◽  
Systemic Amyloidosis ◽  
Attr Amyloidosis ◽  
Cryo Electron Microscopy ◽  
Terminal Fragment ◽  
Amyloid Deposits ◽  
Hereditary Attr Amyloidosis

Abstract ATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 Å cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils.

scholarly journals α-Synuclein polymorphism determines oligodendroglial dysfunction

2021 ◽  
Author(s):  
Benedikt Frieg ◽  
James A Geraets ◽  
Timo Strohaeker ◽  
Christian Dienemann ◽  
Panagiota Mavroeidi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Brain Tissue ◽  
Ex Vivo ◽  
Neurological Diseases ◽  
Alpha Synuclein ◽  
Published Data ◽  
Cryo Electron Microscopy ◽  
Fibril Structure ◽  
Potential Biomarker

Synucleinopathies, such as Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive and unremitting neurological diseases. For both PD and MSA, alpha-synuclein fibril inclusions inside brain cells are neuropathological hallmarks. In addition, amplification of alpha-synuclein fibrils from body fluids is a potential biomarker distinguishing PD from MSA. However, little is known about the structure of alpha-synuclein fibrils amplified from human samples and its connection to alpha-synuclein fibril structure in the human brain. Here we amplified alpha-synuclein fibrils from PD and MSA brain tissue, characterized its seeding potential in oligodendroglia, and determined the 3D structures by cryo-electron microscopy. We show that the alpha-synuclein fibrils from a MSA patient are more potent in recruiting the endogenous alpha-synuclein and evoking a redistribution of TPPP/p25alpha protein in mouse primary oligodendroglial cultures compared to those amplified from a PD patient. Cryo-electron microscopy shows that the PD- and MSA-amplified alpha-synuclein fibrils share a similar protofilament fold but differ in their inter-protofilament interface. The structures of the brain-tissue amplified alpha-synuclein fibrils are also similar to other in vitro and ex vivo alpha-synuclein fibrils. Together with published data, our results suggest that aSyn fibrils differ between PD and MSA in their quaternary arrangement and could further vary between different forms of PD and MSA.

New challenges to image processing posed by cryo-Electron microscopy of single particles

1991 ◽  
Vol 49 ◽  
pp. 422-423
Author(s):  
Joachim Frank
Keyword(s):  
Electron Microscopy ◽  
Phase Contrast ◽  
Particle Orientation ◽  
Single Particles ◽  
Contrast Transfer Function ◽  
Virtual Absence ◽  
Cryo Electron Microscopy ◽  
Spatial Frequencies ◽  
New Challenges ◽  
Particle Images

Compared with images of negatively stained single particle specimens, those obtained by cryo-electron microscopy have the following new features: (a) higher “signal” variability due to a higher variability of particle orientation; (b) reduced signal/noise ratio (S/N); (c) virtual absence of low-spatial-frequency information related to elastic scattering, due to the properties of the phase contrast transfer function (PCTF); and (d) reduced resolution due to the efforts of the microscopist to boost the PCTF at low spatial frequencies, in his attempt to obtain recognizable particle images.

Enhanced information from biological materials through technological improvements in cryo-electron microscopy

1992 ◽  
Vol 50 (1) ◽  
pp. 788-789
Author(s):  
Marc J.C. de Jong ◽  
Wim M. Busing ◽  
Max T. Otten
Keyword(s):  
Electron Microscopy ◽  
Electron Beam ◽  
Biological Materials ◽  
Electron Crystallography ◽  
Cryo Electron Microscopy ◽  
Transmission Electron ◽  
The Many ◽  
Technological Improvements ◽  
Beam Damage

Biological materials damage rapidly in the electron beam, limiting the amount of information that can be obtained in the transmission electron microscope. The discovery that observation at cryo temperatures strongly reduces beam damage (in addition to making it unnecessaiy to use chemical fixatives, dehydration agents and stains, which introduce artefacts) has given an important step forward to preserving the ‘live’ situation and makes it possible to study the relation between function, chemical composition and morphology.Among the many cryo-applications, the most challenging is perhaps the determination of the atomic structure. Henderson and co-workers were able to determine the structure of the purple membrane by electron crystallography, providing an understanding of the membrane's working as a proton pump. As far as understood at present, the main stumbling block in achieving high resolution appears to be a random movement of atoms or molecules in the specimen within a fraction of a second after exposure to the electron beam, which destroys the highest-resolution detail sought.

Study of eukaryotic flagellar components by cryo-electron microscopy

1986 ◽  
Vol 44 ◽  
pp. 98-101
Author(s):  
John M. Murray ◽  
Rob Ward
Keyword(s):  
Electron Microscopy ◽  
Primary Motion ◽  
Cryo Electron Microscopy ◽  
Cross Links ◽  
Cilia And Flagella

The eukaryotic flagellum is constructed from 11 parallel tubular elements arranged as 9 peripheral fibers (doublet microtubules) and 2 central fibers (singlet microtubules). The primary motion generating component has been found to be arranged as axially periodic “arms” bridging the adjacent doublets. The dynein, comprising the arms, has been isolated and characterized from several different cilia and flagella. Various radial and azimuthal cross-links stabilize the axially aligned microtubules, and probably play some role in controlling the form of the flagella beat cycle.

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