3DXD

Crystal structure of the intracellular domain of human APP (T668E mutant) in complex with Fe65-PTB2

3DXD の概要

• エントリーDOI: 10.2210/pdb3dxd/pdb
• 関連するPDBエントリー: 3DXC 3DXE
• 分子名称: Amyloid beta A4 protein-binding family B member 1, Amyloid beta A4 protein (3 entities in total)
• 機能のキーワード: alzheimer's disease, app, aicd, fe65, ptb domain, alzheimer disease, amyloid, apoptosis, cell adhesion, coated pit, disease mutation, endocytosis, glycoprotein, heparin-binding, iron, membrane, metal-binding, notch signaling pathway, phosphoprotein, protease inhibitor, proteoglycan, serine protease inhibitor, transmembrane, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane: O00213; Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 39166.41

構造登録者

Radzimanowski, J.,Sinning, I.,Wild, K. (登録日: 2008-07-24, 公開日: 2008-09-16, 最終更新日: 2024-02-21)

主引用文献

Radzimanowski, J.,Simon, B.,Sattler, M.,Beyreuther, K.,Sinning, I.,Wild, K.
Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.
Embo Rep., 9:1134-1140, 2008

PubMed Abstract: Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. The interaction of the APP C terminus with the adaptor protein Fe65 mediates APP trafficking and signalling, and is thought to regulate APP processing and Abeta generation. We determined the crystal structure of the AICD in complex with the C-terminal phosphotyrosine-binding (PTB) domain of Fe65. The unique interface involves the NPxY PTB-binding motif and two alpha helices. The amino-terminal helix of the AICD is capped by threonine T(668), an Alzheimer disease-relevant phosphorylation site involved in Fe65-binding regulation. The structure together with mutational studies, isothermal titration calorimetry and nuclear magnetic resonance experiments sets the stage for understanding T(668) phosphorylation-dependent complex regulation at a molecular level. A molecular switch model is proposed.

PubMed: 18833287
DOI: 10.1038/embor.2008.188

実験手法

X-RAY DIFFRACTION (2.2 Å)