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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Common core structure of amyloid fibrils by synchrotron X-ray diffraction
M Sunde1, L C Serpell, M Bartlam
1University of Oxford, Rex Richards Building, South Parks Road, Oxford, OX1 3QU, UK.
Journal of Molecular Biology
|November 14, 1997
Summary
Amyloid fibrils, associated with diseases like Alzheimer's, share a common structure. Despite diverse origins, these protein aggregates form a structural superfamily with a shared protofilament substructure.
Area of Science:
- Biochemistry
- Structural Biology
- Pathology
Background:
- Protein misfolding and aggregation into amyloid fibrils are hallmarks of severe diseases such as Alzheimer's disease, diabetes, and transmissible spongiform encephalopathies.
- Despite the lack of sequence homology or structural similarity in their native precursor proteins, amyloid fibrils exhibit consistent morphology and properties across different diseases.
Purpose of the Study:
- To investigate the structural basis for the conserved morphology of amyloid fibrils.
- To determine if amyloid fibrils from various sources share a common structural organization at a high resolution.
Main Methods:
- High-resolution X-ray fiber diffraction was employed using intense synchrotron radiation sources.
- Analysis was performed on six ex vivo amyloid fibril preparations and two synthetic fibril samples.
Main Results:
- All tested amyloid fibril samples produced similar high-resolution X-ray fiber diffraction patterns.
- The diffraction data are consistent with a helical arrangement of beta-sheets running parallel to the fibril axis, with beta-strands oriented perpendicularly.
Conclusions:
- Amyloid fibrils constitute a structural superfamily, irrespective of their precursor proteins.
- A common protofilament substructure underlies the conserved architecture of amyloid fibrils observed across different diseases.
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