7PQP

tau-microtubule structural ensemble based on CryoEM data

Summary for 7PQP

• Entry DOI: 10.2210/pdb7pqp/pdb
• EMDB information: 7522
• Descriptor: Tubulin beta chain, Tubulin alpha-1B chain, Isoform Tau-F of Microtubule-associated protein tau, ... (6 entities in total)
• Functional Keywords: complex, structural protein
• Biological source: Sus scrofa (Pig); More
• Total number of polymer chains: 15
• Total formula weight: 728461.17

Authors

Brotzakis, Z.F.,Vendruscolo, M. (deposition date: 2021-09-18, release date: 2021-12-15, Last modification date: 2024-07-17)

Primary citation

Brotzakis, Z.F.,Lindstedt, P.R.,Taylor, R.J.,Rinauro, D.J.,Gallagher, N.C.T.,Bernardes, G.J.L.,Vendruscolo, M.
A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms.
Acs Cent.Sci., 7:1986-1995, 2021

PubMed Abstract: 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.

PubMed: 34963892
DOI: 10.1021/acscentsci.1c00585

Experimental method

ELECTRON MICROSCOPY (4.1 Å)