3BKC

Crystal structure of anti-amyloid beta FAB WO2 (P21, FormB)

3BKC の概要

• エントリーDOI: 10.2210/pdb3bkc/pdb
• 関連するPDBエントリー: 3BAE 3BKJ 3BKM
• 分子名称: WO2 IgG2a Fab fragment Light Chain Kappa, WO2 IgG2a Fab fragment Heavy Chain, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: abeta, amyloid beta peptide, fab, wo2, alzheimer's disease, immunotherapies, app, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52678.15

構造登録者

Miles, L.A.,Wun, K.S.,Crespi, G.A.,Fodero-Tavoletti, M.,Galatis, D.,Bageley, C.J.,Beyreuther, K.,Masters, C.L.,Cappai, R.,McKinstry, W.J.,Barnham, K.J.,Parker, M.W. (登録日: 2007-12-06, 公開日: 2008-04-15, 最終更新日: 2024-10-30)

主引用文献

Miles, L.A.,Wun, K.S.,Crespi, G.A.,Fodero-Tavoletti, M.T.,Galatis, D.,Bagley, C.J.,Beyreuther, K.,Masters, C.L.,Cappai, R.,McKinstry, W.J.,Barnham, K.J.,Parker, M.W.
Amyloid-beta-anti-amyloid-beta complex structure reveals an extended conformation in the immunodominant B-cell epitope.
J.Mol.Biol., 377:181-192, 2008

PubMed Abstract: Alzheimer's disease (AD) is the most common form of dementia. Amyloid-beta (A beta) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on A beta, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-A beta antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the A beta peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the A beta peptide. The structures reveal the molecular basis for WO2 recognition and binding of A beta. The A beta peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound A beta peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of A beta, such as WO2, hold promise for therapeutic development.

PubMed: 18237744
DOI: 10.1016/j.jmb.2007.12.036

実験手法

X-RAY DIFFRACTION (1.9 Å)