title: Quaternary structure, aggregation and cytotoxicity of transthyretin.
abstract: Transthyretin (TTR) with a Ser112-to-Ile mutation is known to cause amyloidosis with severe cardiomyopathy. We investigated the quaternary structure, aggregation and cytotoxicity of the S112I variant. This variant exists as a dimer at physiological pH, self-assembles into spherical aggregates and induces cell death in human neuroblastoma IMR-32 cells. In addition, we determined the neutron crystal structure of TTR at 2.0 Å resolution. The neutron structure revealed that the hydrogen-bond network involving His88 is important for the stabilization of the dimer-dimer and monomer-monomer interfaces.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan. mineyuki@pha.u-toyama.ac.jp
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawano
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanaka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Niimura
mesh_terms: D000686:Amyloidosis / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D011228:Prealbumin / Q000737:chemistry* / Q000235:genetics; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D011228:Prealbumin