@article{624b9520ba3011ddae57000ea68e967b,
title = "Conformational intermediate of the amyloidogenic protein beta 2-microglobulin at neutral pH.",
abstract = "Aggregation and fibrillation of beta(2)-microglobulin are hallmarks of dialysis-related amyloidosis. We characterize perturbations of the native conformation of beta(2)-microglobulin that may precede fibril formation. For a beta(2)-microglobulin variant cleaved at lysine 58, we show using capillary electrophoresis that two conformers spontaneously exist in aqueous buffers at neutral pH. Upon treatment of wild-type beta(2)-microglobulin with acetonitrile or trifluoroethanol, two conformations were also observed. These conformations were in equilibrium dependent on the sample temperature and the percentage of organic solvent present. Circular dichroism showed a loss of beta-structures and gain of alpha-helices. Reversal to the native conformation occurred when removing the organics. Affinity capillary electrophoresis experiments showed increased specific interactions of the nonnative beta(2)-microglobulin conformation with the dyes 8-anilino-1-naphthalene sulfonic acid and Congo red. The observations may relate to early folding events prior to amyloid fibrillation and facilitate the development of methods to detect and inhibit pro-amyloid protein and peptide conformations.",
author = "Heegaard, {N H} and Sen, {J W} and Kaarsholm, {N C} and Nissen, {Mogens Holst}",
note = "Keywords: Antibodies, Monoclonal; Binding Sites; Circular Dichroism; Congo Red; Humans; Hydrogen-Ion Concentration; Lysine; Peptide Fragments; Protein Conformation; Protein Structure, Secondary; Spectrometry, Mass, Electrospray Ionization; Uremia; Variation (Genetics); beta 2-Microglobulin",
year = "2001",
doi = "10.1074/jbc.M104452200",
language = "English",
volume = "276",
pages = "32657--62",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "35",
}