Transient Diffusive Interactions with a Protein Crowder Affect Aggregation Processes of Superoxide Dismutase 1 β-Barrel
| Autor: | Kenji Sugase, Masahiro Shirakawa, Daichi Morimoto, Erik Walinda, Sarah Leeb, Jens Danielsson, Naoto Iwakawa |
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| Rok vydání: | 2021 |
| Předmět: |
animal diseases
SOD1 010402 general chemistry 01 natural sciences Diffusion Superoxide dismutase Superoxide Dismutase-1 0103 physical sciences Materials Chemistry medicine Humans Physical and Theoretical Chemistry Amyotrophic lateral sclerosis 010304 chemical physics biology Superoxide Dismutase Chemistry Amyotrophic Lateral Sclerosis nutritional and metabolic diseases A protein medicine.disease nervous system diseases 0104 chemical sciences Surfaces Coatings and Films Barrel nervous system Mutation biology.protein Biophysics Muramidase Chemical stability |
| Zdroj: | The Journal of Physical Chemistry B. 125:2521-2532 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.0c11162 |
| Popis: | Aggregate formation of superoxide dismutase 1 (SOD1) inside motor neurons is known as a major factor in onset of amyotrophic lateral sclerosis. The thermodynamic stability of the SOD1 β-barrel has been shown to decrease in crowded environments such as inside a cell, but it remains unclear how the thermodynamics of crowding-induced protein destabilization relate to SOD1 aggregation. Here we have examined the effects of a protein crowder, lysozyme, on fibril aggregate formation of the SOD1 β-barrel. We found that aggregate formation of SOD1 is decelerated even in mildly crowded solutions. Intriguingly, transient diffusive interactions with lysozyme do not significantly affect the static structure of the SOD1 β-barrel but stabilize an alternative excited "invisible" state. The net effect of crowding is to favor species off the aggregation pathway, thereby explaining the decelerated aggregation in the crowded environment. Our observations suggest that the intracellular environment may have a similar negative (inhibitory) effect on fibril formation of other amyloidogenic proteins in living cells. Deciphering how crowded intracellular environments affect aggregation and fibril formation of such disease-associated proteins will probably become central in understanding the exact role of aggregation in the etiology of these enigmatic diseases. |
| Databáze: | OpenAIRE |
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