Structural highlights
Publication Abstract from PubMedIn 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. NMR solution structure of rat abeta(1-16): toward understanding the mechanism of rats' resistance to Alzheimer's disease.,Istrate AN, Tsvetkov PO, Mantsyzov AB, Kulikova AA, Kozin SA, Makarov AA, Polshakov VI Biophys J. 2012 Jan 4;102(1):136-43. Epub 2012 Jan 3. PMID:22225807[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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