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A Hexameric Peptide Barrel as Building Block of Amyloid-β Protofibrils.
- Source :
- Angewandte Chemie; Nov2014, Vol. 126 Issue 47, p12970-12974, 5p
- Publication Year :
- 2014
-
Abstract
- Oligomeric and protofibrillar aggregates formed by the amyloid-β peptide (Aβ) are believed to be involved in the pathology of Alzheimer's disease. Central to Alzheimer pathology is also the fact that the longer Aβ<subscript>42</subscript> peptide is more prone to aggregation than the more prevalent Aβ<subscript>40</subscript>. Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid-state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel-like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C-terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ<subscript>42</subscript> forms oligomers and protofibrils more easily than Aβ<subscript>40</subscript>. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00448249
- Volume :
- 126
- Issue :
- 47
- Database :
- Complementary Index
- Journal :
- Angewandte Chemie
- Publication Type :
- Academic Journal
- Accession number :
- 99368785
- Full Text :
- https://doi.org/10.1002/ange.201406357