Lee, J.-E., Sang, J.C., Rodrigues, M. et al. (9 more authors) (2018) Mapping surface hydrophobicity of α-synuclein oligomers at the nanoscale. Nano Letters, 18 (12). pp. 7494-7501. ISSN 1530-6984
Abstract
Proteins fold into a single structural ensemble but can also misfold into many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role in how they interact with the plasma membrane and cellular organelles, potentially inducing cellular toxicity, however, these properties have not been measured to date due to the lack of suitable methods. Here, we used a spectrally resolved, super-resolution imaging method combined with an environmentally sensitive fluorescent dye to measure the surface hydrophobicity of individual aggregates formed by the protein α-synuclein (αS), whose aggregation is associated with Parkinson’s disease. We show that the surface of soluble oligomers is more hydrophobic than fibrils and populates a diverse range of coexisting states. Overall, our data show that the conversion of oligomers to fibril-like aggregates and ultimately to fibrils results in a reduction in both hydrophobicity and the variation in hydrophobicity. This funneling characteristic of the energy landscape explains many of the observed properties of αS aggregates and may be a common feature of aggregating proteins.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
Keywords: | Super-resolution spectroscopy; spectral imaging; Nile red; hydrophobicity; protein aggregation; alpha-synuclein |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 May 2020 16:19 |
Last Modified: | 01 May 2020 16:19 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acs.nanolett.8b02916 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:160184 |
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