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TitleA Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms.
Journal, issue, pagesACS Cent Sci, Vol. 7, Issue 12, Page 1986-1995, Year 2021
Publish dateDec 22, 2021
AuthorsZ Faidon Brotzakis / Philip R Lindstedt / Ross J Taylor / Dillon J Rinauro / Nicholas C T Gallagher / Gonçalo J L Bernardes / Michele Vendruscolo /
PubMed AbstractTau 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.
External linksACS Cent Sci / PubMed:34963892 / PubMed Central
MethodsEM (single particle)
Resolution4.1 Å
Structure data

PDB-7pqc:
tau-microtubule structural ensemble based on CryoEM data
Method: ELECTRON MICROSCOPY / Resolution: 4.1 Å

PDB-7pqp:
tau-microtubule structural ensemble based on CryoEM data
Method: ELECTRON MICROSCOPY / Resolution: 4.1 Å

Chemicals

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • sus scrofa (pig)
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / Complex

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