Title: De novo design of a biologically active amyloid
Authors: Gallardo, Rodrigo ×
Ramakers, Meine
De Smet, Frederik
Claes, Filip
Khodaparast, Ladan
Khodaparast, Laleh
Couceiro, José
Langenberg, Tobias
Siemons, Maxime
Nyström, Sofie
Young, Laurence J
Laine, Romain F
Young, Lydia
Radaelli, Enrico
Benilova, Iryna
Manoj, Kumar
Staes, An
Desager, Matyas
Beerens, Manu
Vandervoort, Petra
Luttun, Aernout
Gevaert, Kris
Bormans, Guy
Dewerchin, Mieke
Van Eldere, Johan
Carmeliet, Peter
Vande Velde, Greetje
Verfaillie, Catherine
Kaminski, Clemens F
De Strooper, Bart
Hammarström, Per
Nilsson, K Peter R
Serpell, Louise
Schymkowitz, Joost #
Rousseau, Frederic # ×
Issue Date: Nov-2016
Publisher: American Association for the Advancement of Science
Series Title: Science vol:354 issue:6313
Article number: aah4949
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.
ISSN: 0036-8075
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
Laboratory of Clinical Bacteriology and Mycology
Translational Cell & Tissue Research
Radiopharmaceutical Research
Department of Human Genetics - miscellaneous
Biomedical MRI
Switch Laboratory
Molecular and Vascular Biology
Stem Cell Biology and Embryology (+)
× corresponding author
# (joint) last author

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