Abstract
Neurodegenerative and other protein misfolding diseases are associated with the aggregation of a protein, which may be mutated in genetic forms of disease, or the wild type form in late onset sporadic disease. A wide variety of proteins and peptides can be involved, with aggregation originating from a natively folded or a natively unstructured species. Large deposits of amyloid fibrils are typically associated with cell death in late stage pathology. In this review, we illustrate the contributions of cryo-EM and related methods to the structure determination of amyloid fibrils extracted post mortem from patient brains or formed in vitro. We also discuss cell models of protein aggregation and the contributions of electron tomography to understanding the cellular context of aggregation.
🔬 Techniques
✨ Fluorophores
🧪 Sample Preparation
🔬 Cell Lines
🏭 Microscope Brands
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1
Cross-u03b2 structure and tau deposits in Alzheimeru2019s disease brain.
From left to right, the upper panels show a schematic of the u03b2-strand arrangement in the cross-u03b2 core of an amyloid fibril; the AD brain used for cryo-EM; and a Thioflavin-S stained light micr...
Figure 2
Atomic structures of amyloid fibrils, viewed down the fibril axis.
(a) The cross-u03b2 structure, (b) u03b2-helices, (c) a combination of cross-u03b2 and u03b2-helical structural motifs. (a) cross-u03b2 packing between laminated u03b2-sheets is generic and can be for...
Figure 3
Aggregation pathway of Huntingtin exon 1 in cells and in vitro .
(a) Huntingtin exon 1 aggregates (43Q) in the course of conversion from reversible, liquid phase droplets to irreversible fibrous aggregates in a HEK293 cell (reproduced from [ 48* ]. (b,c) The in vit...
Figure 4
Huntingtin aggregates in a cell model.
(a) Tomogram section and (b) corresponding rendered view of a cryo tomogram of a Huntingtin exon 1 aggregate from a FIB-milled lamella of a Hela cell (reproduced from [ 50* ]). Fibrils, blue; ribosome...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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