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

Sci Rep. 2013;3:1302. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Bonding
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal, Humanized
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • bapineuzumab