7pqp

From Proteopedia

tau-microtubule structural ensemble based on CryoEM data

Structural highlights

7pqp is a 15 chain structure with sequence from Homo sapiens and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TBB_PIG Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.

Publication Abstract from PubMed

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.

A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms.,Brotzakis ZF, Lindstedt PR, Taylor RJ, Rinauro DJ, Gallagher NCT, Bernardes GJL, Vendruscolo M ACS Cent Sci. 2021 Dec 22;7(12):1986-1995. doi: 10.1021/acscentsci.1c00585. Epub , 2021 Dec 8. PMID:34963892^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Brotzakis ZF, Lindstedt PR, Taylor RJ, Rinauro DJ, Gallagher NCT, Bernardes GJL, Vendruscolo M. A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms. ACS Cent Sci. 2021 Dec 22;7(12):1986-1995. PMID:34963892 doi:10.1021/acscentsci.1c00585