Possible Existence of α‑Sheets in the Amyloid Fibrils Formed by a TTR105–115 Mutant

Herein, we combine several methods to characterize the fibrils formed by a TTR105–115 mutant in which Leu111 is replaced by the unnatural amino acid aspartic acid 4-methyl ester. We find that this mutant peptide exhibits significantly different aggregation behavior than the wild-type peptide: (1) it...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2018-01, Vol.140 (2), p.629-635
Main Authors: Hilaire, Mary Rose, Ding, Bei, Mukherjee, Debopreeti, Chen, Jianxin, Gai, Feng
Format: Article
Language:English
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Summary:Herein, we combine several methods to characterize the fibrils formed by a TTR105–115 mutant in which Leu111 is replaced by the unnatural amino acid aspartic acid 4-methyl ester. We find that this mutant peptide exhibits significantly different aggregation behavior than the wild-type peptide: (1) it forms fibrils with a much faster rate, (2) its fibrils lack the long-range helical twists observed in TTR105–115 fibrils, (3) its fibrils exhibit a giant far-UV circular dichroism signal, and (4) its fibrils give rise to an unusual amide I′ band consisting of four distinct and sharp peaks. On the basis of these results and also several previous computational studies, we hypothesize that the fibrils formed by this TTR mutant peptide contain both β- and α-sheets.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b09262