SERF engages in a fuzzy complex that accelerates primary nucleation of amyloid proteins.
Proc Natl Acad Sci U S A
; 116(46): 23040-23049, 2019 11 12.
Article
em En
| MEDLINE
| ID: mdl-31659041
ABSTRACT
The assembly of small disordered proteins into highly ordered amyloid fibrils in Alzheimer's and Parkinson's patients is closely associated with dementia and neurodegeneration. Understanding the process of amyloid formation is thus crucial in the development of effective treatments for these devastating neurodegenerative diseases. Recently, a tiny, highly conserved and disordered protein called SERF was discovered to modify amyloid formation in Caenorhabditis elegans and humans. Here, we use kinetics measurements and native ion mobility-mass spectrometry to show that SERF mainly affects the rate of primary nucleation in amyloid formation for the disease-related proteins Aß40 and α-synuclein. SERF's high degree of plasticity enables it to bind various conformations of monomeric Aß40 and α-synuclein to form structurally diverse, fuzzy complexes. This structural diversity persists into early stages of amyloid formation. Our results suggest that amyloid nucleation is considerably more complex than age-related conversion of Aß40 and α-synuclein into single amyloid-prone conformations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Saccharomyces cerevisiae
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Peptídeos beta-Amiloides
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Proteínas de Saccharomyces cerevisiae
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Alfa-Sinucleína
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article