The amyloidogenic variant of ß2-microglobulin, D76N, can readily convert into genuine fibrils under physiological conditions and primes in vitro the fibrillogenesis of the wild-type ß2-microglobulin. By Fourier transformed infrared spectroscopy, we have demonstrated that the amyloid transformation of wild-type ß2-microglobulin can be induced by the variant only after its complete fibrillar conversion. Our current findings are consistent with preliminary data in which we have shown a seeding effect of fibrils formed from D76N or the natural truncated form of ß2-microglobulin lacking the first six N-terminal residues. Interestingly, the hybrid wild-type/variant fibrillar material acquired a thermodynamic stability similar to that of homogenous D76Nß2-microglobulin fibrils and significantly higher than the wild-type homogeneous fibrils prepared at neutral pH in the presence of 20% trifluoroethanol. These results suggest that the surface ofD76Nß2-microglobulin fibrils can favor the transition of the wild-type protein into an amyloid conformation leading to a rapid integration into fibrils. The chaperone crystallin, which is a mild modulator of the lag phase of the variant fibrillogenesis, potently inhibits fibril elongation of the wild-type even once it is absorbed on D76Nß2-microglobulin fibrils.
Natalello, A., Mangione, P., Giorgetti, S., Porcari, R., Marchese, L., Zorzoli, I., et al. (2016). Co-fibrillogenesis of wild-type and D76N β2-microglobulin: The crucial role of fibrillar seeds. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 291(18), 9678-9689.
Citazione: | Natalello, A., Mangione, P., Giorgetti, S., Porcari, R., Marchese, L., Zorzoli, I., et al. (2016). Co-fibrillogenesis of wild-type and D76N β2-microglobulin: The crucial role of fibrillar seeds. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 291(18), 9678-9689. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Presenza di un coautore afferente ad Istituzioni straniere: | Si |
Titolo: | Co-fibrillogenesis of wild-type and D76N β2-microglobulin: The crucial role of fibrillar seeds |
Autori: | Natalello, A; Mangione, P; Giorgetti, S; Porcari, R; Marchese, L; Zorzoli, I; Relini, A; Ami, D; Faravelli, G; Valli, M; Stoppini, M; Doglia, S; Bellotti, V; Raimondi, S |
Autori: | NATALELLO, ANTONINO (Primo) |
Data di pubblicazione: | 2016 |
Lingua: | English |
Rivista: | THE JOURNAL OF BIOLOGICAL CHEMISTRY |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1074/jbc.M116.720573 |
Appare nelle tipologie: | 01 - Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | Licenza | |
---|---|---|---|---|
J. Biol. Chem.-2016-Natalello-9678-89.pdf | Articolo principale | Publisher's version | Open Access Visualizza/Apri |