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