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-Structure paper
タイトル | A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms. |
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ジャーナル・号・ページ | ACS Cent Sci, Vol. 7, Issue 12, Page 1986-1995, Year 2021 |
掲載日 | 2021年12月22日 |
![]() | Z Faidon Brotzakis / Philip R Lindstedt / Ross J Taylor / Dillon J Rinauro / Nicholas C T Gallagher / Gonçalo J L Bernardes / Michele Vendruscolo / ![]() ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 4.1 Å |
構造データ | ![]() PDB-7pqc: ![]() PDB-7pqp: |
化合物 | ![]() ChemComp-GDP: ![]() ChemComp-GTP: ![]() ChemComp-MG: |
由来 |
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![]() | STRUCTURAL PROTEIN / Complex |