2LI9

Metal binding domain of rat beta-amyloid

2LI9 の概要

• エントリーDOI: 10.2210/pdb2li9/pdb
• 関連するPDBエントリー: 1ZE7
• NMR情報: BMRB: 17884
• 分子名称: Amyloid beta A4 protein, ZINC ION (2 entities in total)
• 機能のキーワード: alzheimer's disease, dimer formation, zinc binding, cell adhesion
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P08592
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 3839.41

構造登録者

Polshakov, V.,Istrate, A.,Kozin, S.,Makarov, A. (登録日: 2011-08-25, 公開日: 2012-01-18, 最終更新日: 2024-10-30)

主引用文献

Istrate, A.N.,Tsvetkov, P.O.,Mantsyzov, A.B.,Kulikova, A.A.,Kozin, S.A.,Makarov, A.A.,Polshakov, V.I.
NMR solution structure of rat Abeta(1-16): toward understanding the mechanism of rats' resistance to Alzheimer's disease.
Biophys.J., 102:136-143, 2012

PubMed Abstract: In an attempt to reveal the mechanism of rats' resistance to Alzheimer's disease, we determined the structure of the metal-binding domain 1-16 of rat β-amyloid (rat Aβ(1-16)) in solution in the absence and presence of zinc ions. A zinc-induced dimerization of the domain was detected. The zinc coordination site was found to involve residues His-6 and His-14 of both peptide chains. We used experimental restraints obtained from analyses of NMR and isothermal titration calorimetry data to perform structure calculations. The calculations employed an explicit water environment and a simulated annealing molecular-dynamics protocol followed by quantum-mechanical/molecular-mechanical optimization. We found that the C-tails of the two polypeptide chains of the rat Aβ(1-16) dimer are oriented in opposite directions to each other, which hinders the assembly of rat Aβ dimers into oligomeric aggregates. Thus, the differences in the structure of zinc-binding sites of human and rat Aβ(1-16), their ability to form regular cross-monomer bonds, and the orientation of their hydrophobic C-tails could be responsible for the resistance of rats to Alzheimer's disease.

PubMed: 22225807
DOI: 10.1016/j.bpj.2011.11.4006

実験手法

SOLUTION NMR