The role of water in the primary nucleation of protein amyloid aggregation

10 pags, 1 fig.

Detalles Bibliográficos
Autores: Camino, José D., Gracia, Pablo, Cremades, Nunilo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/248821
Acceso en línea:http://hdl.handle.net/10261/248821
Access Level:acceso abierto
Palabra clave:Amyloid aggregation
Primary nucleation
Water activity
Intrinsically disordered proteins
Homogeneous nucleation
Liquid-liquid phase separation
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spelling The role of water in the primary nucleation of protein amyloid aggregationCamino, José D.Gracia, PabloCremades, NuniloAmyloid aggregationPrimary nucleationWater activityIntrinsically disordered proteinsHomogeneous nucleationLiquid-liquid phase separation10 pags, 1 fig.The understanding of the complex conformational landscape of amyloid aggregation and its modulation by relevant physicochemical and cellular factors is a prerequisite for elucidating some of the molecular basis of pathology in amyloid related diseases, and for developing and evaluating effective disease-specific therapeutics to reduce or eliminate the underlying sources of toxicity in these diseases. Interactions of proteins with solvating water have been long considered to be fundamental in mediating their function and folding; however, the relevance of water in the process of protein amyloid aggregation has been largely overlooked. Here, we provide a perspective on the role water plays in triggering primary amyloid nucleation of intrinsically disordered proteins (IDPs) based on recent experimental evidences. The initiation of amyloid aggregation likely results from the synergistic effect between both protein intermolecular interactions and the properties of the water hydration layer of the protein surface. While the self-assembly of both hydrophobic and hydrophilic IDPs would be thermodynamically favoured due to large water entropy contributions, large desolvation energy barriers are expected, particularly for the nucleation of hydrophilic IDPs. Under highly hydrating conditions, primary nucleation is slow, being facilitated by the presence of nucleation-active surfaces (heterogeneous nucleation). Under conditions of poor water activity, such as those found in the interior of protein droplets generated by liquid-liquid phase separation, however, the desolvation energy barrier is significantly reduced, and nucleation can occur very rapidly in the bulk of the solution (homogeneous nucleation), giving rise to structurally distinct amyloid polymorphs. Water, therefore, plays a key role in modulating the transition free energy of amyloid nucleation, thus governing the initiation of the process, and dictating the type of preferred primary nucleation and the type of amyloid polymorph generated, which could vary depending on the particular microenvironment that the protein molecules encounter in the cell.The authors acknowledge financial support from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the Spanish Ministry of Science, Innovation and Universities (MICIU) and the European Commission (FEDER) (Grants RYC-2012- 12068, BFU2015-64119-P and PGC2018-096335-B-100).Elsevier BVMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/248821reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-64119-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-096335-B-100http://dx.doi.org/10.1016/j.bpc.2020.106520Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2488212026-05-22T06:33:51Z
dc.title.none.fl_str_mv The role of water in the primary nucleation of protein amyloid aggregation
title The role of water in the primary nucleation of protein amyloid aggregation
spellingShingle The role of water in the primary nucleation of protein amyloid aggregation
Camino, José D.
Amyloid aggregation
Primary nucleation
Water activity
Intrinsically disordered proteins
Homogeneous nucleation
Liquid-liquid phase separation
title_short The role of water in the primary nucleation of protein amyloid aggregation
title_full The role of water in the primary nucleation of protein amyloid aggregation
title_fullStr The role of water in the primary nucleation of protein amyloid aggregation
title_full_unstemmed The role of water in the primary nucleation of protein amyloid aggregation
title_sort The role of water in the primary nucleation of protein amyloid aggregation
dc.creator.none.fl_str_mv Camino, José D.
Gracia, Pablo
Cremades, Nunilo
author Camino, José D.
author_facet Camino, José D.
Gracia, Pablo
Cremades, Nunilo
author_role author
author2 Gracia, Pablo
Cremades, Nunilo
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Amyloid aggregation
Primary nucleation
Water activity
Intrinsically disordered proteins
Homogeneous nucleation
Liquid-liquid phase separation
topic Amyloid aggregation
Primary nucleation
Water activity
Intrinsically disordered proteins
Homogeneous nucleation
Liquid-liquid phase separation
description 10 pags, 1 fig.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/248821
url http://hdl.handle.net/10261/248821
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-64119-P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-096335-B-100
http://dx.doi.org/10.1016/j.bpc.2020.106520
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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