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De novo design of a biologically active amyloid
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.
VIB Switch Lab, Belgium; Katholieke University of Leuven, Belgium.
Vise andre og tillknytning
2016 (engelsk)Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 354, nr 6313, s. 720-+Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
AMER ASSOC ADVANCEMENT SCIENCE , 2016. Vol. 354, nr 6313, s. 720-+
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-132985DOI: 10.1126/science.aah4949ISI: 000387326300028PubMedID: 27846578OAI: oai:DiVA.org:liu-132985DiVA, id: diva2:1054744
Merknad

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

Tilgjengelig fra: 2016-12-09 Laget: 2016-12-07 Sist oppdatert: 2019-11-08

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