De novo design of a biologically active amyloid-Reference-Cited by-同舟云学术

De novo design of a biologically active amyloid

Published:2016-11-11 Issue:6313 Volume:354 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Gallardo Rodrigo¹²,Ramakers Meine¹²,De Smet Frederik¹²,Claes Filip¹²,Khodaparast Ladan¹²³,Khodaparast Laleh¹²³,Couceiro José R.¹²,Langenberg Tobias¹²,Siemons Maxime¹²⁴,Nyström Sofie⁵,Young Laurence J.⁶,Laine Romain F.⁶,Young Lydia⁷⁸,Radaelli Enrico⁹¹⁰,Benilova Iryna⁹¹⁰,Kumar Manoj¹¹,Staes An¹²¹³,Desager Matyas¹²⁴,Beerens Manu¹⁴,Vandervoort Petra¹⁴,Luttun Aernout¹⁴,Gevaert Kris¹²¹³,Bormans Guy⁴,Dewerchin Mieke¹⁵¹⁶,Van Eldere Johan³,Carmeliet Peter¹⁵¹⁶,Vande Velde Greetje¹⁷,Verfaillie Catherine¹¹,Kaminski Clemens F.⁶,De Strooper Bart⁹¹⁰,Hammarström Per⁵,Nilsson K. Peter R.⁵,Serpell Louise¹⁸,Schymkowitz Joost¹²,Rousseau Frederic¹²

Affiliation:

1. VIB Switch Laboratory, Leuven, Belgium.

2. Department for Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), Belgium.

3. Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology and Immunology, KU Leuven, Belgium.

4. Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.

5. IFM Department of Chemistry, Linköping University, Linköping, Sweden.

6. Department of Chemical Engineering and Biotechnology, University of Cambridge, New Museums Site, Pembroke Street, Cambridge CB2 3RA, UK.

7. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.

8. School of Molecular and Cellular Biology, University of Leeds, Leeds, UK.

9. VIB Center for the Biology of Disease, 3000 Leuven, Belgium.

10. Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases (LIND), KU Leuven, 3000 Leuven, Belgium.

11. Stem Cell Institute, KU Leuven, Leuven, Belgium.

12. VIB Medical Biotechnology Center, VIB, Ghent, Belgium.

13. Department of Biochemistry, Ghent University, Ghent, Belgium.

14. Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology Research Unit, Endothelial Cell Biology Unit, KU Leuven, B-3000 Leuven, Belgium.

15. Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, B-3000 Leuven, Belgium.

16. Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven B-3000, Belgium.

17. Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

18. School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK.

Abstract

Aggregation by design Amyloid aggregation is driven by short sequences within proteins that self-assemble into characteristic amyloid structures. About 30 human proteins are implicated in amyloid-associated diseases, but many more contain short sequences that are potentially amyloidogenic. Gallardo et al. designed a peptide based on an amyloidogenic sequence in the vascular endothelial growth factor receptor VEGFR2. The peptide induced VEGFR2 to form aggregates with features characteristic of amyloids. Amyloids were toxic only in cells that required VEGFR2 activity, suggesting that the toxicity was due to loss of function of VEGFR2, rather than to inherent toxicity of the aggregates. The peptide inhibited VEGFR2-dependent tumor growth in a mouse tumor model. Science , this issue p. 10.1126/science.aah4949

Funder

European Research Council

ERC

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)

KU Leuven

Wellcome Trust Institutional Strategic Support Fund

The Göran Gustafsson Foundation

The Swedish Research Council