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The trans isomer of Tau peptide is prone to aggregate, and the WW domain of Pin1 drastically decreases its aggregation
Author(s) -
Ikura Teikichi,
Tochio Naoya,
Kawasaki Ryosuke,
Matsuzaki Mizuki,
Narita Akihiro,
Kikumoto Mahito,
UtsunomiyaTate Naoko,
Tate Shinichi,
Ito Nobutoshi
Publication year - 2018
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 - 10.1002/1873-3468.13218
Subject(s) - pin1 , chemistry , isomerase , peptide , cis–trans isomerism , ww domain , protein aggregation , stereochemistry , amyloid (mycology) , phosphorylation , biophysics , biochemistry , enzyme , biology , inorganic chemistry , gene
In Alzheimer's, the disease‐related protein Tau is hyperphosphorylated and aggregates into neurofibrillary tangles (NFT). The cis isomer of the phosphorylated Thr231‐Pro232 has been proposed as a precursor of aggregation (‘Cistauosis’), but this aggregation scheme is not yet completely accepted. Here, we synthesized peptides comprising a phosphorylated region including Thr231‐Pro232 and an aggregation‐core region R1 to investigate isomer‐specific‐aggregation of Tau. The phosphorylated peptide formed amyloid‐like aggregation. This aggregation was observed even in the presence of the catalytic domain of the peptidyl‐prolyl‐isomerase Pin1, which preferentially converts the cis isomer to the trans isomer, but decreased drastically in the presence of the WW domain of Pin1 selectively binding to the trans isomer. These results indicate that the trans isomer is aggregation‐prone and that the WW domain of Pin1 effectively inhibits its aggregation.