Bapineuzumab captures the N-terminus of the alzheimer’s disease amyloid-beta peptide in a helical conformation

 

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.

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Topics: Alzheimer’s disease, Intrinsically disordered proteins, Molecular neuroscience, Nanocrystallography, Monolith–MicroScale Thermophoresis, MST, Proteins, Publications

 

 

 

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