Short disordered protein segment regulates cross-species transmission of a yeast prion.
Nat Chem Biol
; 16(7): 756-765, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32284601
ABSTRACT
Soluble prion proteins contingently encounter foreign prion aggregates, leading to cross-species prion transmission. However, how its efficiency is regulated by structural fluctuation of the host soluble prion protein remains unsolved. In the present study, through the use of two distantly related yeast prion Sup35 proteins, we found that a specific conformation of a short disordered segment governs interspecies prion transmissibility. Using a multidisciplinary approach including high-resolution NMR and molecular dynamics simulation, we identified critical residues within this segment that allow interspecies prion transmission in vitro and in vivo, by locally altering dynamics and conformation of soluble prion proteins. Remarkably, subtle conformational differences caused by a methylene group between asparagine and glutamine sufficed to change the short segment structure and substantially modulate the cross-seeding activity. Thus, our findings uncover how conformational dynamics of the short segment in the host prion protein impacts cross-species prion transmission. More broadly, our study provides mechanistic insights into cross-seeding between heterologous proteins.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asparagina
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Saccharomyces cerevisiae
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Priones
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Factores de Terminación de Péptidos
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Proteínas de Saccharomyces cerevisiae
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Proteínas Intrínsecamente Desordenadas
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Glutamina
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2020
Tipo del documento:
Article