Natalello, A;
Mangione, PP;
Giorgetti, S;
Porcari, R;
Marchese, L;
Zorzoli, I;
Relini, A;
... Raimondi, S; + view all
(2016)
Co-fibrillogenesis of Wild-type and D76N β₂-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS.
Journal of Biological Chemistry
, 291
(18)
pp. 9678-9689.
10.1074/jbc.M116.720573.
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Abstract
The amyloidogenic variant of β2-microglobulin, D76N, can readily convert into genuine fibrils under physiological conditions and primes in vitro the fibrillogenesis of the wild-type β2-microglobulin. By Fourier transformed infrared spectroscopy, we have demonstrated that the amyloid transformation of wild-type β2-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 β2-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 D76N β2-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 of D76N β2-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 D76N β2-microglobulin fibrils.
| Type: | Article |
|---|---|
| Title: | Co-fibrillogenesis of Wild-type and D76N β₂-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1074/jbc.M116.720573 |
| Publisher version: | http://dx.doi.org/10.1074/jbc.M116.720573 |
| Language: | English |
| Additional information: | © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0). |
| Keywords: | amyloid, fibril, Fourier transform IR (FTIR), protein aggregation, protein misfolding, β2-microglobulin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1490493 |
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