His-tag binding by antibody C706 mimics β-amyloid recognition
Article first published online: 14 SEP 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Journal of Molecular Recognition
Volume 24, Issue 4, pages 570–575, July/August 2011
How to Cite
Teplyakov, A., Obmolova, G., Canziani, G., Zhao, Y., Gutshall, L., Jung, S. S. and Gilliland, G. L. (2011), His-tag binding by antibody C706 mimics β-amyloid recognition. J. Mol. Recognit., 24: 570–575. doi: 10.1002/jmr.1069
- Issue published online: 7 APR 2011
- Article first published online: 14 SEP 2010
- Manuscript Revised: 28 JUN 2010
- Manuscript Accepted: 28 JUN 2010
- Manuscript Received: 3 JUN 2010
- Alzheimer's disease;
- monoclonal antibody;
- crystal structure
Alzheimer's disease is a progressive neurodegenerative disease characterized by extracellular deposits of β-amyloid (Aβ) plaques. Aggregation of the Aβ42 peptide leading to plaque formation is believed to play a central role in Alzheimer's disease pathogenesis. Anti-Aβ monoclonal antibodies can reduce amyloid plaques and could possibly be used for immunotherapy. We have developed a monoclonal antibody C706, which recognizes the human Aβ peptide. Here we report the crystal structure of the antibody Fab fragment at 1.7 Å resolution. The structure was determined in two crystal forms, P21 and C2. Although the Fab was crystallized in the presence of Aβ16, no peptide was observed in the crystals. The antigen-binding site is blocked by the hexahistidine tag of another Fab molecule in both crystal forms. The poly-His peptide in an extended conformation occupies a crevice between the light and heavy chains of the variable domain. Two consecutive histidines (His4–His5) stack against tryptophan residues in the central pocket of the antigen-binding surface. In addition, they form hydrogen bonds to the acidic residues at the bottom of the pocket. The mode of his-tag binding by C706 resembles the Aβ recognition by antibodies PFA1 and WO2. All three antibodies recognize the same immunodominant B-cell epitope of Aβ. By similarity, residues Phe–Arg–His of Aβ would be a major portion of the C706 epitope. Copyright © 2010 John Wiley & Sons, Ltd.