Skip to main content
Research article - Peer-reviewed, 2017

Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β

Wahlberg, Elisabet; Rahman, M. Mahafuzur; Lindberg, Hanna; Gunneriusson, Elin; Schmuck, Benjamin; Lendel, Christofer; Sandgren, Mats; Lofblom, John; Stahl, Stefan; Hard, Torleif

Abstract

Protofibrils of the 42 amino acids long amyloid-beta peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer's disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of A beta(42)cc, which is a stable engineered mimic of wild type A beta(42) protofibrils. Several binders were identified that bind A beta(42)cc protofibrils with low nanomolar affinities, and which also recognize wild type A beta(42) protofibrils. Dimeric head-to-tail fusion proteins with subnanomolar binding affinities, and very slow dissociation off-rates, were also constructed. A mapping of the chemical properties of the side chains onto the Affibody scaffold surface reveals three distinct adjacent surface areas of positively charged surface, nonpolar surface and a polar surface, which presumably match a corresponding surface epitope on the protofibrils. The results demonstrate that the engineered A beta(42)cc is a suitable antigen for directed evolution of affinity reagents with specificity for wild type A beta(42) protofibrils.

Published in

Scientific Reports
2017, volume: 7, article number: 5949

Authors' information

Wahlberg, Elisabet
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Wahlberg, Elisabet
Affibody AB
Rahman, Mahafuzur
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Lindberg, Hanna
Royal Institute of Technology (KTH)
Gunneriusson, Elin
Affibody AB
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Lendel, Christofer
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Löfblom, John
Royal Institute of Technology (KTH)
Ståhl, Stefan
Royal Institute of Technology (KTH)
Swedish University of Agricultural Sciences, Department of Molecular Sciences

UKÄ Subject classification

Biochemistry and Molecular Biology

Publication Identifiers

DOI: https://doi.org/10.1038/s41598-017-06377-8

URI (permanent link to this page)

https://res.slu.se/id/publ/90846