Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation
Abstract
Bapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (Aβ) plaques that underlie Alzheimer's disease neuropathology. Here we report the crystal structure of a Fab-Aβ peptide complex that reveals Bapineuzumab surprisingly captures Aβ in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble Aβ(1-40) with a KD of 89 (+/-9) nM. The structure explains the antibody's exquisite selectivity for particular Aβ species and why it cannot recognize N-terminally modified or truncated Aβ peptides.
- Publication:
-
Scientific Reports
- Pub Date:
- February 2013
- DOI:
- 10.1038/srep01302
- Bibcode:
- 2013NatSR...3E1302M