The solution structure of rat Abeta-(1-28) and its interaction with zinc ion: insights into the scarcity of amyloid deposition in aged rat brain.
The amyloid beta-peptide (Abeta) is a major component of insoluble amyloid deposits in Alzheimer's 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 Abeta amyloid deposition has been found in aged rats' brains. Studying the three-dimensional solution structure of rat Abeta-(1-28) and the binding circumstance of Zn(2+) is beneficial to a clear understanding of the potential role of Zn(2+) in Alzheimer-associated neuropathogenesis and to suggest why there is no amyloid deposition in aged rats' brains. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of rat Abeta-(1-28) and the binding constant of Zn(2+) to rat Abeta-(1-28). Our results suggest that (1) the three-dimensional solution structure of rat Abeta-(1-28) is more stable than that of human Abeta-(1-28) in DMSO- d(6) and that a helical region from Glu16 to Val24 exists in the rat Abeta-(1-28); (2) the affinity of Zn(2+) for rat Abeta-(1-28) is lower than that for human Abeta-(1-28) and the NMR data suggest that Arg13, His6, and His14 residues provide the primary binding sites for Zn(2+); and (3) the proper binding of Zn(2+) to rat Abeta-(1-28) can induce the peptide to change to a more stable conformation.
Huang
Jin
J
Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, Nanjing University, 210093 Nanjing, China.
Yao
Yong
Y
Lin
Jun
J
Ye
Yong-Hao
YH
Sun
Wei-Yin
WY
Tang Dagger
Wen-Xia
WX
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000596:Amino Acids / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006801:Humans; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D012996:Solutions; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D007477:Ions; D010446:Peptide Fragments; D012996:Solutions; D015032:Zinc; D004121:Dimethyl Sulfoxide