journal article

Journal Article

Text

Journal of Biological Chemistry. 2012, 287(27), p. 22827-22837

Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol

American Society for Biochemistry and Molecular Biology

English

Text

2012-06

https://doi.org/10.1074/jbc.M111.333310

This research was originally published in the Journal of Biological Chemistry. Eri Chatani, Hisashi Yagi, Hironobu Naiki and Yuji Goto. Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol. J. Biol. Chem. 2012; 287, 22827-22837. © the American Society for Biochemistry and Molecular Biology

The polymorphic property of amyloid structures has been focused on as a molecular basis of the presence and propagation of different phenotypes of amyloid diseases, although little is known about the molecular mechanism for expressing diverse structures from only one protein sequence. Here, we have found that, in combination with an enhancing effect of ultrasonication on nucleation, β2-microglobulin, a protein responsible for dialysis-related amyloidosis, generates distinct fibril conformations in a concentration-dependent manner in the presence of 2,2,2-trifluoroethanol (TFE). Although the newly formed fibrils all exhibited a similar needle-like morphology with an extensive cross-β core, as suggested by Fourier transform infrared absorption spectra, they differed in thioflavin T intensity, extension kinetics, and tryptophan fluorescence spectra even in the same solvents, representing polymorphic structures. The hydrophobic residues seemed to be more exposed in the fibrils originating at higher concentrations of TFE, as indicated by the increased binding of 1-anilinonaphthalene-8-sulfonic acid, suggesting that the modulation of hydrophobic interactions is critical to the production of polymorphic amyloid structures. Interestingly, the fibrils formed at higher TFE concentrations showed significantly higher stability against guanidium hydrochloride, the perturbation of ionic strength, and, furthermore, pressurization. The cross-β structure inside the fibrils seems to have been more idealized, resulting in increased stability when nucleation occurred in the presence of the alcohol, indicating that a weaker contribution of hydrophobic interactions is intrinsically more amenable to the formation of a non-defective amyloid structure.

71281

Polymorphism of β2-Microglobulin Amyloid Fibrils Manifested by Ultrasonication-enhanced Fibril Formation in Trifluoroethanol

American Society for Biochemistry and Molecular Biology

English

2012-06

Journal of Biological Chemistry

287

27

22827

22837

https://doi.org/10.1074/jbc.M111.333310

https://hdl.handle.net/11094/71281