Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils
| Autor: | Gerald P. Gellermann, Karl-Jürgen Halbhuber, Christoph Röcken, Peter Hortschansky, Uwe Horn, Carsten Sachse, Marcus Fändrich, Jürgen Götz, Michael Brodhun, Christian Haupt, Jessica Meinhardt, Ralf P. Friedrich, Gernot Habicht, Karin Wieligmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Amyloid
macromolecular substances Biology Fibril Epitope Antibodies Epitopes Protein structure Peptide Library medicine Animals Humans Peptide library Multidisciplinary Amyloid beta-Peptides Neurodegeneration P3 peptide Biological Sciences medicine.disease protein folding prion neurodegeneration Peptide Fragments Recombinant Proteins Protein Structure Tertiary Biochemistry Biophysics Protein folding Camelids New World |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 104(49): 19232-19237 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|