| Literature DB >> 27846578 |
Rodrigo Gallardo1,2, Meine Ramakers1,2, Frederik De Smet1,2, Filip Claes1,2, Ladan Khodaparast1,2,3, Laleh Khodaparast1,2,3, José R Couceiro1,2, Tobias Langenberg1,2, Maxime Siemons1,2,4, Sofie Nyström5, Laurence J Young6, Romain F Laine6, Lydia Young7,8, Enrico Radaelli9,10, Iryna Benilova9,10, Manoj Kumar11, An Staes12,13, Matyas Desager1,2,4, Manu Beerens14, Petra Vandervoort14, Aernout Luttun14, Kris Gevaert12,13, Guy Bormans4, Mieke Dewerchin15,16, Johan Van Eldere3, Peter Carmeliet15,16, Greetje Vande Velde17, Catherine Verfaillie11, Clemens F Kaminski6, Bart De Strooper9,10, Per Hammarström5, K Peter R Nilsson5, Louise Serpell18, Joost Schymkowitz19,2, Frederic Rousseau19,2.
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.Entities:
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Year: 2016 PMID： 27846578 DOI： 10.1126/science.aah4949
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728