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A hexameric peptide barrel as building block of amyloid-β protofibrils
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Lendel, Christofer, Bjerring, Morten, Dubnovitsky, Anatoly, Kelly, Robert T., Filippov, Andrei, Antzutkin, Oleg N., Nielsen, Niels Chr. and Härd, Torleif (2014) A hexameric peptide barrel as building block of amyloid-β protofibrils. Angewandte Chemie International Edition, Volume 53 (Number 47). pp. 12756-12760. doi:10.1002/anie.201406357 ISSN 1433-7851.
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Official URL: http://dx.doi.org/10.1002/anie.201406357
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 Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40. 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 Aβ42 forms oligomers and protofibrils more easily than Aβ40.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Physics | ||||||||
Journal or Publication Title: | Angewandte Chemie International Edition | ||||||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||||||
ISSN: | 1433-7851 | ||||||||
Official Date: | 19 November 2014 | ||||||||
Dates: |
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Volume: | Volume 53 | ||||||||
Number: | Number 47 | ||||||||
Page Range: | pp. 12756-12760 | ||||||||
DOI: | 10.1002/anie.201406357 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
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