A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
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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7160 |
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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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
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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1799134570285629440 |