Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state.
Nat Commun
; 8(1): 2081, 2017 12 12.
Article
em En
| MEDLINE
| ID: mdl-29234026
ABSTRACT
Protein misfolding and aggregation is increasingly being recognized as a cause of disease. In Alzheimer's disease the amyloid-ß peptide (Aß) misfolds into neurotoxic oligomers and assembles into amyloid fibrils. The Bri2 protein associated with Familial British and Danish dementias contains a BRICHOS domain, which reduces Aß fibrillization as well as neurotoxicity in vitro and in a Drosophila model, but also rescues proteins from irreversible non-fibrillar aggregation. How these different activities are mediated is not known. Here we show that Bri2 BRICHOS monomers potently prevent neuronal network toxicity of Aß, while dimers strongly suppress Aß fibril formation. The dimers assemble into high-molecular-weight oligomers with an apparent two-fold symmetry, which are efficient inhibitors of non-fibrillar protein aggregation. These results indicate that Bri2 BRICHOS affects qualitatively different aspects of protein misfolding and toxicity via different quaternary structures, suggesting a means to generate molecular chaperone diversity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catarata
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Glicoproteínas de Membrana
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Ataxia Cerebelar
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Peptídeos beta-Amiloides
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Angiopatia Amiloide Cerebral Familiar
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Surdez
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Demência
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Agregação Patológica de Proteínas
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article