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

Reference
Article Authors:Luke A Miles; Gabriela A N Crespi; Larissa Doughty; Michael W Parker
Article Title:Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.
Reference Detail
Reference ID:1025596
Abstract:Bapineuzumab is a humanized antibody developed by Pfizer and Johnson & Johnson targeting the amyloid (A) plaques that underlie Alzheimer's disease neuropathology. Here we report the crystal structure of a Fab-A peptide complex that reveals Bapineuzumab surprisingly captures A in a monomeric helical conformation at the N-terminus. Microscale thermophoresis suggests that the Fab binds soluble A(1-40) with a K(D) of 89 (±9) nM. The structure explains the antibody's exquisite selectivity for particular A species and why it cannot recognize N-terminally modified or truncated A peptides.
Affiliations:ACRF Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3056, Australia.
Date:2013
Reference Type:Literature
PubMed ID:23416764
Journal:Sci Rep
Journal Volume:3
Article Pages:1302
Journal ISSN:2045-2322
Article Chemical List:Amyloid beta-Peptides;Antibodies, Monoclonal, Humanized;Peptide Fragments;amyloid beta-protein (1-40);bapineuzumab
Article MeSH List:Alzheimer Disease(metabolism; pathology); Amyloid beta-Peptides(chemistry; metabolism); Antibodies, Monoclonal, Humanized(chemistry; metabolism); Crystallography, X-Ray; Humans; Hydrogen Bonding; Peptide Fragments(chemistry; metabolism); Protein Binding; Protein Structure, Secondary
Curation Last Updated:2015-06-07 20:24:26