Paramore, R., Morgan, G. J., Davis, P. J. et al. (7 more authors) (2012) Mapping local structural perturbations in the native state of stefin B (cystatin B) under amyloid forming conditions. Frontiers in Molecular Neuroscience, 5. 94. ISSN 1662-5099
Abstract
Unlike a number of amyloid-forming proteins, stefins, and in particular stefin B (cystatin B) form amyloids under conditions where the native state predominates. In order to trigger oligomerization processes, the stability of the protein needs to be compromised, favoring structural re-arrangement however, accelerating fibril formation is not a simple function of protein stability. We report here on how optimal conditions for amyloid formation lead to the destabilization of dimeric and tetrameric states of the protein in favor of the monomer. Small, highly localized structural changes can be mapped out that allow us to visualize directly areas of the protein which eventually become responsible for triggering amyloid formation. These regions of the protein overlap with the Cu (II)-binding sites which we identify here for the first time. We hypothesize that in vivo modulators of amyloid formation may act similarly to painstakingly optimized solvent conditions developed in vitro. We discuss these data in the light of current structural models of stefin B amyloid fibrils based on H-exchange data, where the detachment of the helical part and the extension of loops were observed.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012 Paramore, Morgan, Davis, Sharma, Hounslow, Taler-Verčič, Žerovnik, Waltho, Cliff and Staniforth. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. https://creativecommons.org/licenses/by/3.0/ |
Keywords: | Cu (II)-binding; precursors of amyloid; cystatin B; stefin B; proline isomerization |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Mar 2017 12:32 |
Last Modified: | 20 Mar 2017 12:32 |
Published Version: | http://dx.doi.org/10.3389/fnmol.2012.00094 |
Status: | Published |
Publisher: | Frontiers Media |
Refereed: | Yes |
Identification Number: | 10.3389/fnmol.2012.00094 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:113843 |