A carregar...
Publicação
A structural ensemble of a tau-microtubule complex reveals regulatory tau phosphorylation and acetylation mechanisms
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 11.46 MB | Adobe PDF |
Orientador(es)
Resumo(s)
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.
Descrição
© 2021 The Authors. Published by American Chemical Society.
Palavras-chave
Contexto Educativo
Citação
ACS Cent Sci. 2021 Dec 22;7(12):1986-1995
Editora
ACS Publications