Comparative analysis of human and Dutch-type Alzheimer beta-amyloid peptides by infrared spectroscopy and circular dichroism.
The 42 amino acid beta A4 peptide is the major constituent of the senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. While C-terminally truncated variants were shown to be present in normal body fluids, a single Glu-->Gln change in the 39 amino acid form of beta A4 results in accelerated fibril formation in the brains of patients with Dutch-type hereditary cerebral hemorrhage with amyloidosis. In this study we used Fourier-transform infrared and circular dichroism spectroscopies on synthetic peptides to demonstrate that this mutation results in altered secondary structure in membrane mimicking solvents, characterized by a considerably higher beta-structure content for the mutant peptide. Moreover, extreme high and low pH were less effective in eliminating the beta-conformation for the Dutch-variant than for the normal human sequence.
Fabian
H
H
Institute for Biodiagnostics, National Research Council Canada, Winnipeg.
Szendrei
G I
GI
Mantsch
H H
HH
Otvos
L
L
D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000686:Amyloidosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics / Q000473:pathology*; D002942:Circular Dichroism; D005583:Fourier Analysis; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009426:Netherlands; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012377:Rodentia; D017386:Sequence Homology, Amino Acid; D013055:Spectrophotometry, Infrared
D016229:Amyloid beta-Peptides; D010455:Peptides