4HIX

Crystal structure of a humanised 3D6 Fab bound to amyloid beta peptide

Summary for 4HIX

• Entry DOI: 10.2210/pdb4hix/pdb
• Related: 2IPU 3BAE
• Descriptor: Humanized 3D6 Fab heavy chain, Humanized 3D6 Fab light chain, Beta-amyloid protein 40, ... (4 entities in total)
• Functional Keywords: immunoglobulin, immunotherapy candidate, amyloid beta peptide, protein fibril-immune system complex, protein fibril/immune system
• Biological source: homo Sapiens, Mus musculus (human, mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 3
• Total formula weight: 51694.54

Authors

Miles, L.A.,Crespi, G.A.N.,Parker, M.W. (deposition date: 2012-10-12, release date: 2013-03-13, Last modification date: 2024-11-20)

Primary citation

Miles, L.A.,Crespi, G.A.,Doughty, L.,Parker, M.W.
Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.
Sci Rep, 3:1302-1302, 2013

PubMed 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.

PubMed: 23416764
DOI: 10.1038/srep01302

Experimental method

X-RAY DIFFRACTION (2.204 Å)