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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.
Keywords
PROTEIN AGGREGATION, ALPHA-SYNUCLEIN, NEURODEGENERATIVE DISEASES, ALZHEIMERS-DISEASE, GLOBULAR-PROTEINS, A-BETA, SEQUENCE, FIBRILS, SPECIFICITY, PEPTIDES

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Citation

Please use this url to cite or link to this publication:

Chicago
Gallardo, Rodrigo, Meine Ramakers, Frederik De Smet, Filip Claes, Ladan Khodaparast, Laleh Khodaparast, José R Couceiro, et al. 2016. “De Novo Design of a Biologically Active Amyloid.” Science 354 (6313).
APA
Gallardo, R., Ramakers, M., De Smet, F., Claes, F., Khodaparast, L., Khodaparast, L., Couceiro, J. R., et al. (2016). De novo design of a biologically active amyloid. SCIENCE, 354(6313).
Vancouver
1.
Gallardo R, Ramakers M, De Smet F, Claes F, Khodaparast L, Khodaparast L, et al. De novo design of a biologically active amyloid. SCIENCE. 2016;354(6313).
MLA
Gallardo, Rodrigo, Meine Ramakers, Frederik De Smet, et al. “De Novo Design of a Biologically Active Amyloid.” SCIENCE 354.6313 (2016): n. pag. Print.
@article{8508286,
  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.},
  articleno    = {aah4949},
  author       = {Gallardo, Rodrigo and Ramakers, Meine and De Smet, Frederik and Claes, Filip and Khodaparast, Ladan and Khodaparast, Laleh and Couceiro, Jos{\'e} R and Langenberg, Tobias and Siemons, Maxime and Nystr{\"o}m, Sofie and Young, Laurence J and Laine, Romain F and Young, Lydia and Radaelli, Enrico and Benilova, Iryna and Kumar, Manoj and Staes, An and Desager, Matyas and Beerens, Manu and Vandervoort, Petra and Luttun, Aernout and Gevaert, Kris and Bormans, Guy and Dewerchin, Mieke and Van Eldere, Johan and Carmeliet, Peter and Vande Velde, Greetje and Verfaillie, Catherine and Kaminski, Clemens F and De Strooper, Bart and Hammarstr{\"o}m, Per and Nilsson, K Peter R and Serpell, Louise and Schymkowitz, Joost and Rousseau, Frederic},
  issn         = {0036-8075},
  journal      = {SCIENCE},
  keyword      = {PROTEIN AGGREGATION,ALPHA-SYNUCLEIN,NEURODEGENERATIVE DISEASES,ALZHEIMERS-DISEASE,GLOBULAR-PROTEINS,A-BETA,SEQUENCE,FIBRILS,SPECIFICITY,PEPTIDES},
  language     = {eng},
  number       = {6313},
  pages        = {9},
  title        = {De novo design of a biologically active amyloid},
  url          = {http://dx.doi.org/10.1126/science.aah4949},
  volume       = {354},
  year         = {2016},
}

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