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2LI9: Metal binding domain of rat beta-amyloidстатья
- Авторы: Polshakov V., Istrate A., Kozin S., Makarov A.
- Журнал: Worldwide Protein Data Bank
- Год издания: 2012
- DOI: 10.2210/pdb2li9/pdb
- 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 beta-amyloid (rat Abeta(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 Abeta(1-16) dimer are oriented in opposite directions to each other, which hinders the assembly of rat Abeta dimers into oligomeric aggregates. Thus, the differences in the structure of zinc-binding sites of human and rat Abeta(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