3IFP

X-ray structure of amyloid beta peptide:antibody (Abeta1-7:12B4) complex

3IFP の概要

• エントリーDOI: 10.2210/pdb3ifp/pdb
• 関連するPDBエントリー: 3IFL 3IFN 3IFO
• 分子名称: 12B4 FAB antibody heavy chain, 12B4 FAB antibody light chain, Amyloid beta A4 protein (3 entities in total)
• 機能のキーワード: antibody, amyloid beta peptide, immune system
• 由来する生物種: Mus musculus (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: 12
• 化学式量合計: 198621.06

構造登録者

Weis, W.I.,Feinberg, H.,Basi, G.S.,Schenk, D. (登録日: 2009-07-24, 公開日: 2009-11-17, 最終更新日: 2024-10-30)

主引用文献

Basi, G.S.,Feinberg, H.,Oshidari, F.,Anderson, J.,Barbour, R.,Baker, J.,Comery, T.A.,Diep, L.,Gill, D.,Johnson-Wood, K.,Goel, A.,Grantcharova, K.,Lee, M.,Li, J.,Partridge, A.,Griswold-Prenner, I.,Piot, N.,Walker, D.,Widom, A.,Pangalos, M.N.,Seubert, P.,Jacobsen, J.S.,Schenk, D.,Weis, W.I.
Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease.
J.Biol.Chem., 285:3417-3427, 2010

PubMed Abstract: Immunotherapy targeting of amyloid beta (Abeta) peptide in transgenic mouse models of Alzheimer disease (AD) has been widely demonstrated to resolve amyloid deposition as well as associated neuronal, glial, and inflammatory pathologies. These successes have provided the basis for ongoing clinical trials of immunotherapy for treatment of AD in humans. Acute as well as chronic Abeta-targeted immunotherapy has also been demonstrated to reverse Abeta-related behavioral deficits assessing memory in AD transgenic mouse models. We observe that three antibodies targeting the same linear epitope of Abeta, Abeta(3-7), differ in their ability to reverse contextual fear deficits in Tg2576 mice in an acute testing paradigm. Reversal of contextual fear deficit by the antibodies does not correlate with in vitro recognition of Abeta in a consistent or correlative manner. To better define differences in antigen recognition at the atomic level, we determined crystal structures of Fab fragments in complex with Abeta. The conformation of the Abeta peptide recognized by all three antibodies was highly related and is also remarkably similar to that observed in independently reported Abeta:antibody crystal structures. Sequence and structural differences between the antibodies, particularly in CDR3 of the heavy chain variable region, are proposed to account for differing in vivo properties of the antibodies under study. These findings provide a structural basis for immunotherapeutic strategies targeting Abeta species postulated to underlie cognitive deficits in AD.

PubMed: 19923222
DOI: 10.1074/jbc.M109.045187

実験手法

X-RAY DIFFRACTION (2.95 Å)