| Autor: |
Gümral, D., Fogolari, F., Corazza, A., Viglino, P., Giorgetti, S., Stoppini, M., Esposito, G. |
| Přispěvatelé: |
Gümral, D., Fogolari, F., Corazza, A., Viglino, P., Giorgetti, S., Stoppini, M., Esposito, G., Yeditepe Üniversitesi |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
|
| Popis: |
The amyloid pathology associated with long-term haemodialysis is due to the deposition of ß2-microglobulin, the non-polymorphic light chain of class I major histocompatibility complex, that accumulates at bone joints into amyloid fibrils. Several lines of evidence show the relevance of the tryptophan residue at position 60 for the fibrillogenic transition of the protein. A comparative 15N NMR relaxation analysis is presented for wild-type human ß2-microglobulin and W60G ß2- microglobulin, i.e. the mutant with a glycyne replacing the natural tryptophan residue at position 60. The experimental data, collected at 11.4 T and 310 K, were analyzed by means of the reduced spectral density approach. Molecular dynamics (MD) simulations and corresponding thermodynamic integration, together with hydrodynamic calculations were performed to support data interpretation. The analysis results for the mutant protein are consistent with a reduced aggregation with respect to the wild-type counterpart, as a consequence of an increased conformational rigidity probed by either NMR relaxation and MD simulations. Although dynamics in solution is other than fibrillar competence, the assessed properties of the mutant protein can be related with its reduced ability of forming fibrils when seeded in 20% trifluoroethanol. Copyright © 2013 John Wiley & Sons, Ltd. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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