Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
KTH, School of Biotechnology (BIO), Protein Technology.
Show others and affiliations
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 5949Article in journal (Refereed) Published
Abstract [en]

Protofibrils of the 42 amino acids long amyloid-β 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 Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils. Several binders were identified that bind Aβ42cc protofibrils with low nanomolar affinities, and which also recognize wild type Aβ42 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 Aβ42cc is a suitable antigen for directed evolution of affinity reagents with specificity for wild type Aβ42 protofibrils.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 7, no 1, article id 5949
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-212186DOI: 10.1038/s41598-017-06377-8ISI: 000405907800003Scopus ID: 2-s2.0-85025123694OAI: oai:DiVA.org:kth-212186DiVA, id: diva2:1134194
Note

QC 20170818

Available from: 2017-08-18 Created: 2017-08-18 Last updated: 2017-09-12Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textScopus

Search in DiVA

By author/editor
Lindberg, HannaLendel, ChristoferLöfblom, JohnStåhl, Stefan
By organisation
Protein TechnologyApplied Physical Chemistry
In the same journal
Scientific Reports
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 50 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf