Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils

Habicht G., Haupt C., Friedrich R.P., Hortschansky P., Sachse C., Meinhardt J., Wieligmann K., Gellermann G.P., Brodhun M., Gotz J., Halbhuber K.-J., Rocken C., Horn U. and Fandrich M. (2007) Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils. Proceedings of the National Academy of Sciences of the United States of America, 104 49: 19232-19237. doi:10.1073/pnas.0703793104


Author Habicht G.
Haupt C.
Friedrich R.P.
Hortschansky P.
Sachse C.
Meinhardt J.
Wieligmann K.
Gellermann G.P.
Brodhun M.
Gotz J.
Halbhuber K.-J.
Rocken C.
Horn U.
Fandrich M.
Title Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2007-12-04
Sub-type Article (original research)
DOI 10.1073/pnas.0703793104
Volume 104
Issue 49
Start page 19232
End page 19237
Total pages 6
Language eng
Subject 1311 Genetics
1000 General
Abstract The formation of amyloid fibrils is a common biochemical characteristic that occurs in Alzheimer's disease and several other amyloidoses. The unifying structural feature of amyloid fibrils is their specific type of β-sheet conformation that differentiates these fibrils from the products of normal protein folding reactions. Here we describe the generation of an antibody domain, termed B10, that recognizes an amyloid-specific and conformationally defined epitope. This antibody domain was selected by phage-display from a recombinant library of camelid antibody domains. Surface plasmon resonance, immunoblots, and immunohistochemistry show that this antibody domain distinguishes Aβ amyloid fibrils from disaggregated Aβ peptide as well as from specific Aβ oligomers. The antibody domain possesses functional activity in preventing the formation of mature amyloid fibrils by stabilizing Aβ protofibrils. These data suggest possible applications of B10 in the detection of amyloid fibrils or in the modulation of their formation.
Keyword Neurodegeneration
Prion
Protein folding
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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Citation counts: TR Web of Science Citation Count  Cited 140 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 145 times in Scopus Article | Citations
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