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 journalArticlepeer-review

25 Citations (Scopus)


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
Issue number9
Publication statusPublished - Mar 8 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry


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