3UMH

X-ray structure of the E2 domain of the human amyloid precursor protein (APP) in complex with cadmium

3UMH の概要

• エントリーDOI: 10.2210/pdb3umh/pdb
• 関連するPDBエントリー: 3UMI 3UMK
• 分子名称: Amyloid beta A4 protein, ACETATE ION, CADMIUM ION, ... (4 entities in total)
• 機能のキーワード: metal binding site, metal binding, cell surface, secretory pathway, metal binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26192.19

構造登録者

Dahms, S.O.,Konnig, I.,Roeser, D.,Guhrs, K.H.,Than, M.E. (登録日: 2011-11-13, 公開日: 2012-01-25, 最終更新日: 2024-02-28)

主引用文献

Dahms, S.O.,Konnig, I.,Roeser, D.,Guhrs, K.H.,Mayer, M.C.,Kaden, D.,Multhaup, G.,Than, M.E.
Metal Binding Dictates Conformation and Function of the Amyloid Precursor Protein (APP) E2 Domain.
J.Mol.Biol., 416:438-452, 2012

PubMed Abstract: The amyloid precursor protein (APP) and its neurotoxic cleavage product Aβ are key players in the development of Alzheimer's disease and appear essential for neuronal development and cell homeostasis in mammals. Proteolytic processing of APP is influenced by metal ions, protein ligands and its oligomerization state. However, the structural basis and functional mechanism of APP regulation are hitherto largely unknown. Here we identified a metal-dependent molecular switch located within the E2 domain of APP containing four evolutionary highly conserved histidine residues. Three X-ray structures of the metal-bound molecule were solved at 2.6-2.0 Å resolution. Using protein crystallographic and biochemical methods, we characterized this novel high-affinity binding site within the E2 domain that binds competitively to copper and zinc at physiological concentrations. Metal-specific coordination spheres induce large conformational changes and enforce distinct structural states, most likely regulating the physiological function of APP and its processing in Alzheimer's disease.

PubMed: 22245578
DOI: 10.1016/j.jmb.2011.12.057

実験手法

X-RAY DIFFRACTION (2 Å)