Cu/Zn-superoxide dismutase forms fibrillar hydrogels in a pH-dependent manner via a water-rich extended intermediate state
Autor: | Hironobu Eguchi, Naoto Oba, Tadashi Inoue, Yoshiaki Furukawa, Daisaku Yoshihara, Ichihashi Motoko, Keiichiro Suzuki, Haruhiko Sakiyama, Eiichi Tokuda, Michiru Wagatsuma, Noriko Fujiwara |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Protein Denaturation Conformational change lcsh:Medicine Sodium Chloride Biochemistry Physical Chemistry Molecular Self Assembly chemistry.chemical_compound Superoxide Dismutase-1 Materials Physics Chemical Precipitation Denaturation (biochemistry) lcsh:Science Materials chemistry.chemical_classification Multidisciplinary Viscosity Chemistry Physics Chemical Reactions Classical Mechanics Hydrogels Hydrogen-Ion Concentration Recombinant Proteins Deformation Physical Sciences Self-healing hydrogels Agarose Thioflavin Research Article Amyloid Globular protein Amorphous Solids Materials Science Viscoelastic Substances macromolecular substances Fibril Precipitates 03 medical and health sciences Humans Benzothiazoles Damage Mechanics lcsh:R Water Biology and Life Sciences Proteins Acoustics Quartz crystal microbalance Kinetics 030104 developmental biology Chemical Properties Mixtures Amyloid Proteins Biophysics lcsh:Q Globular Proteins Protein Multimerization Gels |
Zdroj: | PLoS ONE, Vol 13, Iss 10, p e0205090 (2018) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Under certain conditions, amyloid-like fibrils can develop into three-dimensional networks and form hydrogels by a self-assembly process. When Cu/Zn superoxide dismutase (SOD1), an anti-oxidative enzyme, undergoes misfolding, fibrillar aggregates are formed, which are a hallmark of a certain form of familial amyotrophic lateral sclerosis (ALS). However, the issue of whether SOD1 fibrils can be assembled into hydrogels remains to be tested. Here, we show that the SOD1 polypeptides undergo hydrogelation accompanied by the formation of thioflavin T-positive fibrils at pH 3.0 and 4.0, but not at pH 5.0 where precipitates are formed. The results of viscoelastic analyses indicate that the properties of SOD1 hydrogels (2%) were similar to and slightly more fragile than a 0.25% agarose gel. In addition, monitoring by a quartz crystal microbalance with admittance analysis showed that the denaturing of immobilized SOD1 on a sensor under the hydrogelation conditions at pH 3.0 and 4.0 resulted in an increase in the effective acoustic thickness from ~3.3 nm (a folded rigid form) to ~50 and ~100 nm (an extended water-rich state), respectively. In contrast, when SOD1 was denatured under the same conditions at pH 5.0, a compact water-poor state with an effective acoustic thickness of ~10 nm was formed. The addition of physiological concentrations of NaCl to the pH 4.0 sample induced a further extension of the SOD1 with larger amounts of water molecules (with an effective acoustic thickness of ~200 nm) but suppressed hydrogel formation. These results suggest that different denatured intermediate states of the protein before self-assembly play a major role in determining the characteristics of the resulting aggregates and that a conformational change to a suitable level of extended water-rich intermediate state before and/or during intermolecular assembling is required for fibrillation and hydrogelation in the case of globular proteins. |
Databáze: | OpenAIRE |
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