Cited by 130Alzheimer's disease research and treatmentsMonoclonal and Polyclonal Antibodies ResearchProtein Structure and Dynamics

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

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Miles, Luke A., Crespi, Gabriela A. N., Doughty, Larissa, Parker, Michael W.·2013·Scientific Reports

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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Authors
Miles, L. A., Crespi, G. A. N., Doughty, L., & Parker, M. W.
Affiliations
  • Australian Cancer Research Foundation (AU)
  • The University of Melbourne (AU)
Corresponding author
Parker, Michael W.
Venue
Scientific Reports
Published
2013-02-18
Volume
3
Issue
1
Pages
1302-1302
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2033373102
Cited by
130
References
30
Citations by year
2026: 2 · 2025: 9 · 2024: 13 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 7 · 2015: 10 · 2014: 14 · 2013: 4
FWCI
8.10
Type
journal article
Language
en
Update notices
erratum (2013-04-08)
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
Funders
  • Judith Jane Mason and Harold Stannett Williams Memorial Foundation
  • Australian Cancer Research Foundation
  • Australian Synchrotron
  • Medical Research Council
  • National Health and Medical Research Council (1021935)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
bapineuzumab, amyloid-beta, Alzheimer's disease, crystal structure, helical conformation, N-terminus, antibody specificity, amyloid plaques, Aβ(1-40), microscale thermophoresis
MeSH terms
Alzheimer Disease, Humans, Hydrogen Bonding, Peptide Fragments, Protein Binding, Amyloid beta-Peptides, Protein Structure, Secondary, Crystallography, X-Ray, Antibodies, Monoclonal, Humanized

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