De novo design of a biologically active amyloidVIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
University of Cambridge, England; University of Leeds, England; University of Leeds, England.
University of Cambridge, England.
University of Cambridge, England; University of Leeds, England; University of Leeds, England.
VIB Centre Biol Disease, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
VIB Centre Biol Disease, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium.
VIB, Belgium; University of Ghent, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium.
VIB, Belgium; University of Ghent, Belgium.
Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium; VIB, Belgium.
Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium; VIB, Belgium.
Katholieke University of Leuven, Belgium.
Katholieke University of Leuven, Belgium.
University of Cambridge, England.
VIB Centre Biol Disease, Belgium; Katholieke University of Leuven, Belgium; Katholieke University of Leuven, Belgium.
University of Sussex, England.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium.
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2016 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 354, no 6313, p. 720-+Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2016. Vol. 354, no 6313, p. 720-+
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-132985DOI: 10.1126/science.aah4949ISI: 000387326300028PubMedID: 27846578OAI: oai:DiVA.org:liu-132985DiVA, id: diva2:1054744
Note
Funding Agencies|European Research Council (ERC) under the European Union, ERC [647458]; VIB; Industrial Research Funds of KU Leuven (IOF); Funds for Scientific Research Flanders (FWO); Flanders Institute for Science and Technology (IWT); Federal Office for Scientific Affairs of Belgium (Belspo) [IUAP P7/16]; FWO; KU Leuven [PF/10/014]; Wellcome Trust Institutional Strategic Support Fund (ISSF) [015615/Z/14/Z]; Biotechnology and Biological Sciences Research Council through its Research Equipment Initiative scheme [BB/E012558/1]; Goran Gustafsson Foundation; Swedish Research Council; Swedish Alzheimer Foundation; Flemish government; AXA Research grant; Marie Sklodowska-Curie Individual Fellowship under the European Union [H2020-MSCA-IF-2014-ST]; KU Leuven Stem Cell Programme
2016-12-092016-12-072019-11-08