A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms

Detalhes bibliográficos
Autor(a) principal: Brotzakis, Z. Faidon
Data de Publicação: 2021
Outros Autores: Lindstedt, Philip R., Taylor, Ross J., Rinauro, Dillon J., Gallagher, Nicholas C. T., Bernardes, Gonçalo J. L., Vendruscolo, Michele
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/50736
Resumo: © 2021 The Authors. Published by American Chemical Society.
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spelling A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms© 2021 The Authors. Published by American Chemical Society.Tau is a microtubule-associated protein that regulates the stability of microtubules. We use metainference cryoelectron microscopy, an integrative structural biology approach, to determine an ensemble of conformations representing the structure and dynamics of a tau-microtubule complex comprising the entire microtubule-binding region of tau (residues 202-395). We thus identify the ground state of the complex and a series of excited states of lower populations. A comparison of the interactions in these different states reveals positions along the tau sequence that are important to determine the overall stability of the tau-microtubule complex. This analysis leads to the identification of positions where phosphorylation and acetylation events have destabilizing effects, which we validate by using site-specific post-translationally modified tau variants obtained by chemical mutagenesis. Taken together, these results illustrate how the simultaneous determination of ground and excited states of macromolecular complexes reveals functional and regulatory mechanisms.Z.F.B. would like to acknowledge the Federation of European Biochemical Societies (FEBS) for financial support through a long-term fellowship. R.J.T. is supported by the Biotechnology and Biological Sciences Research Council (BBSRC; BB/M011194), and G.J.L.B. is a Royal Society University Research Fellow (URF/R/180019).ACS PublicationsRepositório da Universidade de LisboaBrotzakis, Z. FaidonLindstedt, Philip R.Taylor, Ross J.Rinauro, Dillon J.Gallagher, Nicholas C. T.Bernardes, Gonçalo J. L.Vendruscolo, Michele2022-01-07T12:34:12Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50736engACS Cent Sci. 2021 Dec 22;7(12):1986-199510.1021/acscentsci.1c005852374-7951info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:04Zoai:repositorio.ul.pt:10451/50736Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:08.212640Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
title A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
spellingShingle A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
Brotzakis, Z. Faidon
title_short A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
title_full A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
title_fullStr A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
title_full_unstemmed A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
title_sort A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
author Brotzakis, Z. Faidon
author_facet Brotzakis, Z. Faidon
Lindstedt, Philip R.
Taylor, Ross J.
Rinauro, Dillon J.
Gallagher, Nicholas C. T.
Bernardes, Gonçalo J. L.
Vendruscolo, Michele
author_role author
author2 Lindstedt, Philip R.
Taylor, Ross J.
Rinauro, Dillon J.
Gallagher, Nicholas C. T.
Bernardes, Gonçalo J. L.
Vendruscolo, Michele
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Brotzakis, Z. Faidon
Lindstedt, Philip R.
Taylor, Ross J.
Rinauro, Dillon J.
Gallagher, Nicholas C. T.
Bernardes, Gonçalo J. L.
Vendruscolo, Michele
description © 2021 The Authors. Published by American Chemical Society.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2022-01-07T12:34:12Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50736
url http://hdl.handle.net/10451/50736
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Cent Sci. 2021 Dec 22;7(12):1986-1995
10.1021/acscentsci.1c00585
2374-7951
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv ACS Publications
publisher.none.fl_str_mv ACS Publications
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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