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Updated: Oct 1, 2026
Amyloid and the Cross-Beta Architecture
Published on: February 13, 2026
Conformation of beta 2-microglobulin amyloid fibrils analyzed by reduction of the disulfide bond
Dong-Pyo Hong1, Masayo Gozu, Kazuhiro Hasegawa
1Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Abstract:
Beta2-microglobulin (beta2-m), a major component of dialysis-related amyloid fibrils, has an intrachain disulfide bond buried inside the native structure. We examined the conformation of beta2-m amyloid fibrils by analyzing the reactivity of the disulfide bond to a reducing reagent, dithiothreitol. Although the disulfide bond in the native structure was highly protected from reduction, the disulfide bonds in the amyloid fibrils prepared at pH 2.5 were progressively reduced at pH 8.5 by 50 mm dithiothreitol. Because beta2-m amyloid fibrils prepared under acidic conditions have been known to depolymerize at a neutral pH, we examined the relation between depolymerization and reduction of the disulfide bond. The results indicate that the disulfide bonds in the amyloid fibrils were protected from reduction, and the reduction occurred during depolymerization. On the other hand, the disulfide bonds of immature filaments, the thin and flexible filaments prepared under conditions of high salt at pH 2.5, were reduced at pH 8.5 more readily than those of amyloid fibrils, suggesting that the disulfide bonds are exposed to the solvent. Taken together, the disulfide bond once exposed to the solvent upon acid denaturation may be progressively buried in the interior of the amyloid fibrils during its formation.
Insights
The disulfide bond in beta2-microglobulin (beta2-m) amyloid fibrils becomes buried during formation. Reduction of this bond occurs during depolymerization, not fibril assembly.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Beta2-microglobulin (beta2-m) is a key component of dialysis-related amyloid fibrils.
- Native beta2-m possesses an intrachain disulfide bond protected within its structure.
Purpose of the Study:
- To investigate the conformational changes of beta2-m amyloid fibrils.
- To analyze the accessibility and reactivity of the disulfide bond during fibril formation and depolymerization.
Main Methods:
- Studied the reactivity of the disulfide bond in beta2-m amyloid fibrils using the reducing agent dithiothreitol.
- Compared disulfide bond reduction in mature fibrils versus immature filaments.
- Examined the relationship between depolymerization and disulfide bond reduction at different pH levels.
Main Results:
- Disulfide bonds in beta2-m amyloid fibrils prepared at acidic pH were progressively reduced at neutral pH during depolymerization.
- Immature beta2-m filaments showed more readily reduced disulfide bonds compared to mature fibrils, indicating solvent exposure.
- Disulfide bonds appear to become buried within the amyloid fibril structure as it forms.
Conclusions:
- The disulfide bond's accessibility changes during beta2-m amyloid fibril formation and depolymerization.
- Acid denaturation exposes the disulfide bond, which is subsequently buried as fibrils mature.
- Disulfide bond reduction is linked to the depolymerization process of beta2-m amyloid fibrils.
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