title: Conformational dynamics of beta(2)-microglobulin analyzed by reduction and reoxidation of the disulfide bond.
abstract: Although native beta(2)-microglobulin (beta2-m), the light chain of the major histocompatibility complex class I antigen, assumes an immunoglobulin domain fold, it is also found as a major component of dialysis-related amyloid fibrils. In the amyloid fibrils, the conformation of beta2-m is considered to be largely different from that of the native state, and a monomeric denatured form is likely to be a precursor to the amyloid fibril. To obtain insight into the conformational dynamics of beta2-m leading to the formation of amyloid fibrils, we studied the reduction and reoxidation of the disulfide bond by reduced and oxidized dithiothreitol, respectively, and the effects on the reduction of the chaperonin GroEL, a model protein that might destabilize the native state of beta2-m. We show that beta2-m occasionally unfolds into a denatured form even under physiological conditions and that this transition is promoted upon interaction with GroEL. The results imply that in vivo interactions of beta2-m with other proteins or membrane components could destabilize its native structure, thus stabilizing the amyloid precursor.
authors.affiliation: Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Cooperation, 3-2 Yamadaoka, Suita, Osaka 565-0871.
authors.forename: Masayo
authors.initials: M
authors.lastname: Gozu
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ohhashi
authors.forename: Masaru
authors.initials: M
authors.lastname: Hoshino
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000682:Amyloid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D004220:Disulfides; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D003545:Cysteine