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NMR Solution Structure of Rat A beta(1-16): Toward Understanding the Mechanism of Rats’ Resistance to Alzheimer’s Diseaseстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Istrate Andrey N., Tsvetkov Philipp O., Mantsyzov Alexey B., Kulikova Alexandra A., Kozin Sergey A., Alexander A Makarov, Polshakov Vladimir I.
- Журнал: Biophysical Journal
- Том: 102
- Номер: 1
- Год издания: 2012
- Издательство: Biophysical Society
- Местоположение издательства: United States
- Первая страница: 136
- Последняя страница: 143
- DOI: 10.1016/j.bpj.2011.11.4006
- Аннотация: 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.
- Добавил в систему: Польшаков Владимир Иванович