A beta-Hairpin-Binding Protein for Three Different Disease-Related Amyloidogenic Proteins

Sammanfattning

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.

Nyckelord

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

Publicerad i

ChemBioChem
2015, volym: 16, nummer: 3, sidor: 411-414
Utgivare: WILEY-V C H VERLAG GMBH

SLU författare

• Härd, Torleif

  • Institutionen för kemi och bioteknologi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Biokemi och molekylärbiologi
Biokatalys och enzymteknik

Publikationens identifierare

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

Permanent länk till denna sida (URI)

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