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Amyloidogenicity of rodent and human βA4 sequences
Author(s) -
Dyrks Thomas,
Dyrks Elke,
L. Masters Colin,
Beyreuther Konrad
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81399-k
Subject(s) - tyrosine , histidine , amyloid (mycology) , chemistry , biochemistry , methionine , amino acid , amino acid residue , peptide sequence , rodent , biology , gene , ecology , inorganic chemistry
Previously we have shown that aggregation of the C‐terminal 100 residues (A4CT) of the βA4 amyloid protein precursor (APP) and also of βA4 itself depends on the presence of metal‐catalyzed oxidation systems [T. Dyrks et al. (1988) EMBO J. 7, 949‐957]. We showed that aggregation of the amyloidogenic peptides induced by radical generation systems requires amino acid oxidation and protein cross‐linking. Here we report that aggregation of A4CT and βA4 induced by radical generation systems involves oxidation of histidine, tyrosine and methionine residues. The roden βA4 sequence lacking the single tyrosine and one of the three histidine residues of human βA4 and a βA4 variant in which the tyrosine and the three histidine residues were replaced showed a reduced tendency for aggregation. Thus our results may explain why βA4 amyloid deposits could so far not been detected in the rodent brain.