7CJV
Solution structure of monomeric superoxide dismutase 1 with an additional mutation H46W in a dilute environment
Summary for 7CJV
| Entry DOI | 10.2210/pdb7cjv/pdb |
| NMR Information | BMRB: 36359 |
| Descriptor | Monomeric Human Cu,Zn Superoxide dismutase (1 entity in total) |
| Functional Keywords | dismutase, monomer, amyloid, oxidoreductase |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 11038.35 |
| Authors | Iwakawa, N.,Morimoto, D.,Walinda, E.,Danielsson, J.,Shirakawa, M.,Sugase, K. (deposition date: 2020-07-14, release date: 2021-05-26, Last modification date: 2024-05-15) |
| Primary citation | Iwakawa, N.,Morimoto, D.,Walinda, E.,Leeb, S.,Shirakawa, M.,Danielsson, J.,Sugase, K. Transient Diffusive Interactions with a Protein Crowder Affect Aggregation Processes of Superoxide Dismutase 1 beta-Barrel. J.Phys.Chem.B, 125:2521-2532, 2021 Cited by PubMed Abstract: 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. PubMed: 33657322DOI: 10.1021/acs.jpcb.0c11162 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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