Dimeric transthyretin variant assembles into spherical neurotoxins

Kimiaki Matsubara, Mineyuki Mizuguchi, Kouhei Igarashi, Yoshinori Shinohara, Makoto Takeuchi, Atsushi Matsuura, Takayuki Saitoh, Yoshihiro Mori, Hiroyuki Shinoda, Keiichi Kawano

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Familial amyloidotic polyneuropathy is a hereditary autosomal-dominant disease in which the deposited transthyretin fibrils are derived from amyloidogenic mutation. We investigated structure and stability of a human Ser112Ile transthyretin variant and showed that the Ser112Ile variant exists as a dimer having nonnative tertiary structure at physiological pH. In addition, the dimeric Ser112Ile assembles into a spherical aggregate and exerts cytotoxicity in a human neuroblastoma cell line. Our results suggest the importance of an unstable dimeric structure in forming spherical aggregates that will induce cell death.

Original languageEnglish
Pages (from-to)3280-3288
Number of pages9
JournalBiochemistry
Volume44
Issue number9
DOIs
Publication statusPublished - Mar 8 2005

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Prealbumin
Neurotoxins
Polyneuropathies
Cell death
Cytotoxicity
Neuroblastoma
Dimers
Cell Death
Cells
Cell Line
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Matsubara, K., Mizuguchi, M., Igarashi, K., Shinohara, Y., Takeuchi, M., Matsuura, A., ... Kawano, K. (2005). Dimeric transthyretin variant assembles into spherical neurotoxins. Biochemistry, 44(9), 3280-3288. https://doi.org/10.1021/bi048838c

Dimeric transthyretin variant assembles into spherical neurotoxins. / Matsubara, Kimiaki; Mizuguchi, Mineyuki; Igarashi, Kouhei; Shinohara, Yoshinori; Takeuchi, Makoto; Matsuura, Atsushi; Saitoh, Takayuki; Mori, Yoshihiro; Shinoda, Hiroyuki; Kawano, Keiichi.

In: Biochemistry, Vol. 44, No. 9, 08.03.2005, p. 3280-3288.

Research output: Contribution to journalArticle

Matsubara, K, Mizuguchi, M, Igarashi, K, Shinohara, Y, Takeuchi, M, Matsuura, A, Saitoh, T, Mori, Y, Shinoda, H & Kawano, K 2005, 'Dimeric transthyretin variant assembles into spherical neurotoxins', Biochemistry, vol. 44, no. 9, pp. 3280-3288. https://doi.org/10.1021/bi048838c
Matsubara K, Mizuguchi M, Igarashi K, Shinohara Y, Takeuchi M, Matsuura A et al. Dimeric transthyretin variant assembles into spherical neurotoxins. Biochemistry. 2005 Mar 8;44(9):3280-3288. https://doi.org/10.1021/bi048838c
Matsubara, Kimiaki ; Mizuguchi, Mineyuki ; Igarashi, Kouhei ; Shinohara, Yoshinori ; Takeuchi, Makoto ; Matsuura, Atsushi ; Saitoh, Takayuki ; Mori, Yoshihiro ; Shinoda, Hiroyuki ; Kawano, Keiichi. / Dimeric transthyretin variant assembles into spherical neurotoxins. In: Biochemistry. 2005 ; Vol. 44, No. 9. pp. 3280-3288.
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