Toxic fibrillar oligomers of amyloid-β have cross-β structure
| Autor: | Cong Liu, David Eisenberg, James C. Stroud, Poh K. Teng |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Circular dichroism Amyloid beta-Peptides Multidisciplinary Morphology (linguistics) Amyloid Amyloid β Superhelix Chemistry Circular Dichroism macromolecular substances Biological Sciences Peptide Fragments Protein Structure Secondary Microscopy Electron Crystallography Protein structure X-Ray Diffraction Spectroscopy Fourier Transform Infrared mental disorders Side chain Molecule |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:7717-7722 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Although amyloid fibers are found in neurodegenerative diseases, evidence points to soluble oligomers of amyloid-forming proteins as the cytotoxic species. Here, we establish that our preparation of toxic amyloid-β 1–42 (Abeta42) fibrillar oligomers (TABFOs) shares with mature amyloid fibrils the cross-β structure, in which adjacent β-sheets adhere by interpenetration of protein side chains. We study the structure and properties of TABFOs by powder X-ray diffraction, EM, circular dichroism, FTIR spectroscopy, chromatography, conformational antibodies, and celluar toxicity. In TABFOs, Abeta42 molecules stack into short protofilaments consisting of pairs of helical β-sheets that wrap around each other to form a superhelix. Wrapping results in a hole along the superhelix axis, providing insight into how Abeta may form pathogenic amyloid pores. Our model is consistent with numerous properties of Abeta42 fibrillar oligomers, including heterogenous size, ability to seed new populations of fibrillar oligomers, and fiber-like morphology. |
| Databáze: | OpenAIRE |
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