Biophysical Analyses of the Transthyretin Variants, Tyr114His and Tyr116Ser, Associated with Familial Amyloidotic Polyneuropathy

Yoshinori Shinohara, Mineyuki Mizuguchi, Kimiaki Matsubara, Makoto Takeuchi, Atsushi Matsuura, Takahiro Aoki, Kouhei Igarashi, Hatsumi Nagadome, Yoshihiro Terada*, Keiichi Kawano

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

22 被引用数 (Scopus)

抄録

The familial amyloidotic polyneuropathy is strictly associated with point mutations in the coding region of the transthyretin gene. Here, we focused on the mutations in the monomer-monomer and dimer-dimer interaction site of the transthyretin tetramer. The naturally occurring amyloidogenic Tyr114His (Y114H) and Tyr116Ser (Y116S) variants formed more amyloid fibrils than the wild-type transthyretin, nonamyloidogenic Tyr116Val (Y116V) variant, and other amyloidogenic variants in previous studies. The secondary, tertiary, and quaternary structural stabilities of the Y114H and Y116S variants were compared with those of the wild-type transthyretin and nonamyloidogenic Y116V variant. The unfolding data indicated that the amyloidogenic Y114H and Y116S mutations reduced the stability of the secondary, tertiary, and quaternary structure. Our results also indicated that the unfolding of Y114H and Y116S is less cooperative than that of the wild-type transthyretin. Moreover, the tetramer of the amyloidogenic variants dissociated to the monomer even at pH 7.0, indicating the importance of Tyr114 and Tyr116 in strengthening the contacts between monomers and/or dimers of the transthyretin molecule.

本文言語英語
ページ(範囲)15053-15060
ページ数8
ジャーナルBiochemistry
42
51
DOI
出版ステータス出版済み - 2003/12/30

ASJC Scopus 主題領域

  • 生化学

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