Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA

Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven...

Descripción completa

Detalles Bibliográficos
Autores: Camero, Sergio, Benítez, María J., Cuadros, Raquel, Hernández Pérez, Félix, Ávila, Jesús, Jiménez, Juan S.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/126336
Acceso en línea:http://hdl.handle.net/10261/126336
Access Level:acceso abierto
id ES_8f9d0aade373ec2f8a103f4c1345bc36
oai_identifier_str oai:digital.csic.es:10261/126336
network_acronym_str ES
network_name_str España
repository_id_str
spelling Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNACamero, SergioBenítez, María J.Cuadros, RaquelHernández Pérez, FélixÁvila, JesúsJiménez, Juan S.Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are addressing the physicochemical nature of DNA-Tau interaction including the plausible influence of phosphorylation. By means of surface plasmon resonance (SPR) we measured the equilibrium constant and the free energy, enthalpy and entropy changes associated to the Tau-DNA complex formation. Our results show that unphosphorylated Tau binding to DNA is reversible. This fact is in agreement with the protective role attributed to nuclear Tau, which stops binding to DNA once the insult is over. According to our thermodynamic data, oscillations in the concentration of dephosphorylated Tau available to DNA must be the variable determining the extent of Tau binding and DNA protection. In addition, thermodynamics of the interaction suggest that hydrophobicity must represent an important contribution to the stability of the Tau-DNA complex. SPR results together with those from Tau expression in HEK cells show that phosphorylation induces changes in Tau protein which prevent it from binding to DNA. The phosphorylation-dependent regulation of DNA binding is analogous to the Tau-microtubules binding inhibition induced by phosphorylation. Our results suggest that hydrophobicity may control Tau location and DNA interaction and that impairment of this Tau-DNA interaction, due to Tau hyperphosphorylation, could contribute to Alzheimer's pathogenesis. © 2014 Camero et al.Spanish Government and Comunidad de Madrid. CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades NeurodegenerativasPeer ReviewedPublic Library of ScienceComunidad de MadridCentro de Investigación Biomédica en Red Enfermedades Raras (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520142015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/126336reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1263362026-05-22T06:33:51Z
dc.title.none.fl_str_mv Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
title Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
spellingShingle Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
Camero, Sergio
title_short Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
title_full Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
title_fullStr Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
title_full_unstemmed Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
title_sort Thermodynamics of the interaction between Alzheimer's disease related Tau protein and DNA
dc.creator.none.fl_str_mv Camero, Sergio
Benítez, María J.
Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Jiménez, Juan S.
author Camero, Sergio
author_facet Camero, Sergio
Benítez, María J.
Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Jiménez, Juan S.
author_role author
author2 Benítez, María J.
Cuadros, Raquel
Hernández Pérez, Félix
Ávila, Jesús
Jiménez, Juan S.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Centro de Investigación Biomédica en Red Enfermedades Raras (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are addressing the physicochemical nature of DNA-Tau interaction including the plausible influence of phosphorylation. By means of surface plasmon resonance (SPR) we measured the equilibrium constant and the free energy, enthalpy and entropy changes associated to the Tau-DNA complex formation. Our results show that unphosphorylated Tau binding to DNA is reversible. This fact is in agreement with the protective role attributed to nuclear Tau, which stops binding to DNA once the insult is over. According to our thermodynamic data, oscillations in the concentration of dephosphorylated Tau available to DNA must be the variable determining the extent of Tau binding and DNA protection. In addition, thermodynamics of the interaction suggest that hydrophobicity must represent an important contribution to the stability of the Tau-DNA complex. SPR results together with those from Tau expression in HEK cells show that phosphorylation induces changes in Tau protein which prevent it from binding to DNA. The phosphorylation-dependent regulation of DNA binding is analogous to the Tau-microtubules binding inhibition induced by phosphorylation. Our results suggest that hydrophobicity may control Tau location and DNA interaction and that impairment of this Tau-DNA interaction, due to Tau hyperphosphorylation, could contribute to Alzheimer's pathogenesis. © 2014 Camero et al.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
2015
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/10261/126336
url http://hdl.handle.net/10261/126336
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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
_version_ 1869413226481975297
score 15,811543

Similares en LA Referencia