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

Wahlberg, Elisabet and Rahman, Mahafuzur and Lindberg, Hanna and Gunneriusson, Elin and Schmuck, Benjamin and Lendel, Christofer and Sandgren, Mats and Löfblom, John and Ståhl, Stefan and Härd, Torleif (2017). Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β. Scientific Reports. 7:5949, 1-15
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Official URL: http://dx.doi.org/10.1038/s41598-017-06377-8

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.

Authors/Creators:Wahlberg, Elisabet and Rahman, Mahafuzur and Lindberg, Hanna and Gunneriusson, Elin and Schmuck, Benjamin and Lendel, Christofer and Sandgren, Mats and Löfblom, John and Ståhl, Stefan and Härd, Torleif
Title:Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
Series/Journal:Scientific Reports (2045-2322)
Year of publishing :2017
Volume:7
Number:5949
Page range:1-15
Number of Pages:10
Publisher:Springer Nature
ISSN:2045-2322
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X50 Chemistry
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:biotechnology, molecular biology
Additional ID:
Type of IDID
Web of Science (WoS)000405907800003
ID Code:14876
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:10 Jan 2018 07:21
Metadata Last Modified:11 Jan 2018 11:39

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