Gallardo, R, Ramakers, M, De Smet, F et al. (32 more authors) (2016) De novo design of a biologically active amyloid. Science, 354 (6313). aah4949. ISSN 0036-8075
Abstract
Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional—determined by VEGFR2 loss of function in a biological context in which target protein function is essential.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, American Association for the Advancement of Science. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science, 354 (6313), on 11 November 2016, DOI: 10.1126/science.aah4949. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Feb 2017 10:24 |
Last Modified: | 16 Jan 2018 06:56 |
Published Version: | https://doi.org/10.1126/science.aah4949 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Identification Number: | 10.1126/science.aah4949 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112582 |