The solution structure of rat A(beta)-(1–28) and its interaction with zinc ion: insights into the scarcity of amyloid deposition in aged rat brain

The amyloid (beta)-peptide (A(beta)) is a major component of insoluble amyloid deposits in Alzheimerrsquos disease, and the ability of the (beta)-peptide to exist in different conformations is dependent on residues 1–28 [(beta)-(1–28)]. However, different from humans, no A(beta) amyloid deposition has been found in aged ratsrsquo brains. Studying the three-dimensional solution structure of rat A(beta)-(1– 28) and the binding circumstance of Zn2+ is beneficial to a clear understanding of the potential role of Zn2+ in Alzheimer-associated neuropathogenesis and to suggest why there is no amyloid deposition in aged ratsrsquo brains. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of rat A(beta)-(1–28) and the binding constant of Zn2+ to rat A(beta)(1–28). Our results suggest that (1) the three-dimensional solution structure of rat A(beta)-(1–28) is more stable than that of human A(beta)-(1–28) in DMSO-d6 and that a helical region from Glu16 to Val24 exists in the rat A(beta)-(1–28); (2) the affinity of Zn2+ for rat A(beta)-(1–28) is lower than that for human A(beta)-(1–28) and the NMR data suggest that Arg13, His6, and His14 residues provide the primary binding sites for Zn2+; and (3) the proper binding of Zn2+ to rat A(beta)-(1–28) can induce the peptide to change to a more stable conformation.