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

doi:10.1021/bi048838c

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

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25 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 language	English
Pages (from-to)	3280-3288
Number of pages	9
Journal	Biochemistry
Volume	44
Issue number	9
DOIs	https://doi.org/10.1021/bi048838c
Publication status	Published - Mar 8 2005

All Science Journal Classification (ASJC) codes

Biochemistry

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10.1021/bi048838c

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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.",

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

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T1 - Dimeric transthyretin variant assembles into spherical neurotoxins

AU - Matsubara, Kimiaki

AU - Mizuguchi, Mineyuki

AU - Igarashi, Kouhei

AU - Shinohara, Yoshinori

AU - Takeuchi, Makoto

AU - Matsuura, Atsushi

AU - Saitoh, Takayuki

AU - Mori, Yoshihiro

AU - Shinoda, Hiroyuki

AU - Kawano, Keiichi

PY - 2005/3/8

Y1 - 2005/3/8

N2 - 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.

AB - 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.

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Dimeric transthyretin variant assembles into spherical neurotoxins

Abstract

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