Luke A. Miles, Gabriela A. N. Crespi, Larissa Doughty & Michael W. Parker
Scientific Reports
2013 vol: 3 Article number: 1302 doi: 10.1038/srep01302
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 K(D) 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.
Topics: Alzheimer’s disease, Intrinsically disordered proteins, Molecular neuroscience, Nanocrystallography, Monolith–MicroScale Thermophoresis, MST, Proteins, Publications
