Amyloid cores in prion domains: Key regulators for prion conformational conversion.

Despite the significant efforts devoted to decipher the particular protein features that encode for a prion or prion-like behavior, they are still poorly understood. The well-characterized yeast prions constitute an ideal model system to address this question, because, in these proteins, the prion a...

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Detalles Bibliográficos
Autores: Fernández MR, Batlle C, Gil-García M, Ventura S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p18908
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18908
Access Level:acceso abierto
Palabra clave:*Q/N-rich domains
*amyloids
*prion forming domains
*prion-like proteins
*protein intrinsic disorder
*yeast prions
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spelling Amyloid cores in prion domains: Key regulators for prion conformational conversion.Fernández MRBatlle CGil-García MVentura S*Q/N-rich domains*amyloids*prion forming domains*prion-like proteins*protein intrinsic disorder*yeast prionsDespite the significant efforts devoted to decipher the particular protein features that encode for a prion or prion-like behavior, they are still poorly understood. The well-characterized yeast prions constitute an ideal model system to address this question, because, in these proteins, the prion activity can be univocally assigned to a specific region of their sequence, known as the prion forming domain (PFD). These PFDs are intrinsically disordered, relatively long and, in many cases, of low complexity, being enriched in glutamine/asparagine residues. Computational analyses have identified a significant number of proteins having similar domains in the human proteome. The compositional bias of these regions plays an important role in the transition of the prions to the amyloid state. However, it is difficult to explain how composition alone can account for the formation of specific contacts that position correctly PFDs and provide the enthalpic force to compensate for the large entropic cost of immobilizing these domains in the initial assemblies. We have hypothesized that short, sequence-specific, amyloid cores embedded in PFDs can perform these functions and, accordingly, act as preferential nucleation centers in both spontaneous and seeded aggregation. We have shown that the implementation of this concept in a prediction algorithm allows to score the prion propensities of putative PFDs with high accuracy. Recently, we have provided experimental evidence for the existence of such amyloid cores in the PFDs of Sup35, Ure2, Swi1, and Mot3 yeast prions. The fibrils formed by these short stretches may recognize and promote the aggregation of the complete proteins inside cells, being thus a promising tool for targeted protein inactivation.TAYLOR & FRANCIS INC2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18908PrionISSN: 19336896ISSNe: 1933690Xreponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p189082026-05-27T12:37:41Z
dc.title.none.fl_str_mv Amyloid cores in prion domains: Key regulators for prion conformational conversion.
title Amyloid cores in prion domains: Key regulators for prion conformational conversion.
spellingShingle Amyloid cores in prion domains: Key regulators for prion conformational conversion.
Fernández MR
*Q/N-rich domains
*amyloids
*prion forming domains
*prion-like proteins
*protein intrinsic disorder
*yeast prions
title_short Amyloid cores in prion domains: Key regulators for prion conformational conversion.
title_full Amyloid cores in prion domains: Key regulators for prion conformational conversion.
title_fullStr Amyloid cores in prion domains: Key regulators for prion conformational conversion.
title_full_unstemmed Amyloid cores in prion domains: Key regulators for prion conformational conversion.
title_sort Amyloid cores in prion domains: Key regulators for prion conformational conversion.
dc.creator.none.fl_str_mv Fernández MR
Batlle C
Gil-García M
Ventura S
author Fernández MR
author_facet Fernández MR
Batlle C
Gil-García M
Ventura S
author_role author
author2 Batlle C
Gil-García M
Ventura S
author2_role author
author
author
dc.subject.none.fl_str_mv *Q/N-rich domains
*amyloids
*prion forming domains
*prion-like proteins
*protein intrinsic disorder
*yeast prions
topic *Q/N-rich domains
*amyloids
*prion forming domains
*prion-like proteins
*protein intrinsic disorder
*yeast prions
description Despite the significant efforts devoted to decipher the particular protein features that encode for a prion or prion-like behavior, they are still poorly understood. The well-characterized yeast prions constitute an ideal model system to address this question, because, in these proteins, the prion activity can be univocally assigned to a specific region of their sequence, known as the prion forming domain (PFD). These PFDs are intrinsically disordered, relatively long and, in many cases, of low complexity, being enriched in glutamine/asparagine residues. Computational analyses have identified a significant number of proteins having similar domains in the human proteome. The compositional bias of these regions plays an important role in the transition of the prions to the amyloid state. However, it is difficult to explain how composition alone can account for the formation of specific contacts that position correctly PFDs and provide the enthalpic force to compensate for the large entropic cost of immobilizing these domains in the initial assemblies. We have hypothesized that short, sequence-specific, amyloid cores embedded in PFDs can perform these functions and, accordingly, act as preferential nucleation centers in both spontaneous and seeded aggregation. We have shown that the implementation of this concept in a prediction algorithm allows to score the prion propensities of putative PFDs with high accuracy. Recently, we have provided experimental evidence for the existence of such amyloid cores in the PFDs of Sup35, Ure2, Swi1, and Mot3 yeast prions. The fibrils formed by these short stretches may recognize and promote the aggregation of the complete proteins inside cells, being thus a promising tool for targeted protein inactivation.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18908
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18908
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv TAYLOR & FRANCIS INC
publisher.none.fl_str_mv TAYLOR & FRANCIS INC
dc.source.none.fl_str_mv Prion
ISSN: 19336896
ISSNe: 1933690X
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
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repository.mail.fl_str_mv
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