Abstract

Amyloidogenic proteins share a propensity to convert to the beta-structure-rich amyloid state that is associated with the progression of several protein-misfolding disorders. Here we show that a single engineered beta-hairpin-binding protein, the beta-wrapin AS10, binds monomers of three different amyloidogenic proteins, that is, amyloid-beta peptide, alpha-synuclein, and islet amyloid polypeptide, with sub-micromolar affinity. AS10 binding inhibits the aggregation and toxicity of all three proteins. The results demonstrate common conformational preferences and related binding sites in a subset of the amyloidogenic proteins. These commonalities enable the generation of multispecific monomer-binding agents.

Keywords

amyloids; intrinsically disordered proteins; molecular recognition; protein aggregation; protein engineering

Published in

ChemBioChem
2015, Volume: 16, number: 3, pages: 411-414
Publisher: WILEY-V C H VERLAG GMBH

SLU Authors

• Härd, Torleif

  • The Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Biochemistry and Molecular Biology
Biocatalysis and Enzyme Technology


Publication identifier

DOI: https://doi.org/10.1002/cbic.201402552

Permanent link to this page (URI)

https://res.slu.se/id/publ/66723