Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.
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ABSTRACT:
SUBMITTER: Miles LA
PROVIDER: S-EPMC3575012 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.
Miles Luke A LA Crespi Gabriela A N GA Doughty Larissa L Parker Michael W MW
Scientific reports 20130101
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 par ...[more]
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