2FMA

Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'small unit cell' form, atomic resolution

2FMA の概要

• エントリーDOI: 10.2210/pdb2fma/pdb
• 関連するPDBエントリー: 1OWT 2FJZ 2FK1 2FK2 2FK3 2FKL
• 分子名称: Amyloid beta A4 protein precursor, GLYCEROL (3 entities in total)
• 機能のキーワード: alpha-beta two-layered sandwich, 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: 6941.02

構造登録者

Kong, G.K.-W. (登録日: 2006-01-08, 公開日: 2007-01-16, 最終更新日: 2024-10-09)

主引用文献

Kong, G.K.,Adams, J.J.,Cappai, R.,Parker, M.W.
Structure of Alzheimer's disease amyloid precursor protein copper-binding domain at atomic resolution.
Acta Crystallogr.,Sect.F, 63:819-824, 2007

PubMed Abstract: Amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease, as its cleavage generates the Abeta peptide that is toxic to cells. APP is able to bind Cu2+ and reduce it to Cu+ through its copper-binding domain (CuBD). The interaction between Cu2+ and APP leads to a decrease in Abeta production and to alleviation of the symptoms of the disease in mouse models. Structural studies of CuBD have been undertaken in order to better understand the mechanism behind the process. Here, the crystal structure of CuBD in the metal-free form determined to ultrahigh resolution (0.85 A) is reported. The structure shows that the copper-binding residues of CuBD are rather rigid but that Met170, which is thought to be the electron source for Cu2+ reduction, adopts two different side-chain conformations. These observations shed light on the copper-binding and redox mechanisms of CuBD. The structure of CuBD at atomic resolution provides an accurate framework for structure-based design of molecules that will deplete Abeta production.

PubMed: 17909280
DOI: 10.1107/S1744309107041139

実験手法

X-RAY DIFFRACTION (0.85 Å)