7PQP

tau-microtubule structural ensemble based on CryoEM data

7PQP の概要

• エントリーDOI: 10.2210/pdb7pqp/pdb
• EMDBエントリー: 7522
• 分子名称: Tubulin beta chain, Tubulin alpha-1B chain, Isoform Tau-F of Microtubule-associated protein tau, ... (6 entities in total)
• 機能のキーワード: complex, structural protein
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 728461.17

構造登録者

Brotzakis, Z.F.,Vendruscolo, M. (登録日: 2021-09-18, 公開日: 2021-12-15, 最終更新日: 2024-07-17)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.1 Å)