4HIX

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

4HIX の概要

• エントリーDOI: 10.2210/pdb4hix/pdb
• 関連するPDBエントリー: 2IPU 3BAE
• 分子名称: Humanized 3D6 Fab heavy chain, Humanized 3D6 Fab light chain, Beta-amyloid protein 40, ... (4 entities in total)
• 機能のキーワード: immunoglobulin, immunotherapy candidate, amyloid beta peptide, protein fibril-immune system complex, protein fibril/immune system
• 由来する生物種: homo Sapiens, Mus musculus (human, mouse); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 51694.54

構造登録者

Miles, L.A.,Crespi, G.A.N.,Parker, M.W. (登録日: 2012-10-12, 公開日: 2013-03-13, 最終更新日: 2014-03-19)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.204 Å)