Title |
De novo design of a biologically active amyloid
|
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Published in |
Science, November 2016
|
DOI | 10.1126/science.aah4949 |
Pubmed ID | |
Authors |
Rodrigo Gallardo, Meine Ramakers, Frederik De Smet, Filip Claes, Ladan Khodaparast, Laleh Khodaparast, José R Couceiro, Tobias Langenberg, Maxime Siemons, Sofie Nyström, Laurence J Young, Romain F Laine, Lydia Young, Enrico Radaelli, Iryna Benilova, Manoj Kumar, An Staes, Matyas Desager, Manu Beerens, Petra Vandervoort, Aernout Luttun, Kris Gevaert, Guy Bormans, Mieke Dewerchin, Johan Van Eldere, Peter Carmeliet, Greetje Vande Velde, Catherine Verfaillie, Clemens F Kaminski, Bart De Strooper, Per Hammarström, K Peter R Nilsson, Louise Serpell, Joost Schymkowitz, Frederic Rousseau |
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. |
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Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 9 | 11% |
Belgium | 8 | 10% |
Spain | 3 | 4% |
India | 2 | 2% |
United Kingdom | 2 | 2% |
France | 2 | 2% |
Austria | 1 | 1% |
Djibouti | 1 | 1% |
Afghanistan | 1 | 1% |
Other | 9 | 11% |
Unknown | 44 | 54% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 54 | 66% |
Scientists | 21 | 26% |
Science communicators (journalists, bloggers, editors) | 4 | 5% |
Practitioners (doctors, other healthcare professionals) | 3 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 2% |
China | 2 | <1% |
United Kingdom | 1 | <1% |
Switzerland | 1 | <1% |
Spain | 1 | <1% |
France | 1 | <1% |
Unknown | 238 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 59 | 24% |
Student > Ph. D. Student | 54 | 22% |
Student > Master | 28 | 11% |
Student > Bachelor | 15 | 6% |
Other | 14 | 6% |
Other | 40 | 16% |
Unknown | 38 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 69 | 28% |
Agricultural and Biological Sciences | 48 | 19% |
Chemistry | 21 | 8% |
Medicine and Dentistry | 14 | 6% |
Neuroscience | 12 | 5% |
Other | 35 | 14% |
Unknown | 49 | 20% |