Co-fibrillogenesis of Wild-type and D76N ß2-Microglobulin: THE CRUCIAL ROLE OF FIBRILLAR SEEDS.
J Biol Chem
; 291(18): 9678-89, 2016 Apr 29.
Article
em En
| MEDLINE
| ID: mdl-26921323
ABSTRACT
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 D76N ß2-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 ß2-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 ß2-microglobulin fibrils.
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Base de dados:
MEDLINE
Assunto principal:
Microglobulina beta-2
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Mutação de Sentido Incorreto
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Agregação Patológica de Proteínas
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Amiloide
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article