Hiding in plain sight: Complex interaction patterns between Tau and 14-3-3zeta protein variants

Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Sports Studies. It includes Faculty of Science. Official publication website can be found on muni.cz.
Authors

CRHA Radek KOZELEKOVÁ Aneta HOFROVÁ Alena IĽKOVIČOVÁ Lucia GAŠPARIK Norbert KADEŘÁVEK Pavel HRITZ Jozef

Year of publication 2024
Type Article in Periodical
Magazine / Source INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S0141813024016064?via%3Dihub
Doi http://dx.doi.org/10.1016/j.ijbiomac.2024.130802
Keywords Tau protein;14-3-3 zeta protein;Phosphorylation;Interaction;NMR;Cross-linking
Attached files
Description Tau protein is an intrinsically disordered protein that plays a key role in Alzheimer's disease (AD). In brains of AD patients, Tau occurs abnormally phosphorylated and aggregated in neurofibrillary tangles (NFTs). Together with Tau, 14-3-3 proteins - abundant cytosolic dimeric proteins - were found colocalized in the NFTs. However, so far, the molecular mechanism of the process leading to pathological changes in Tau structure as well as the direct involvement of 14-3-3 proteins are not well understood. Here, we aimed to reveal the effects of phosphorylation by protein kinase A (PKA) on Tau structural preferences and provide better insight into the interaction between Tau and 14-3-3 proteins. We also addressed the impact of monomerization-inducing phosphorylation of 14-3-3 at S58 on the binding to Tau protein. Using multidimensional nuclear magnetic resonance spectroscopy (NMR), chemical cross-linking analyzed by mass spectrometry (MS) and PAGE, we unveiled differences in their binding affinity, stoichiometry, and interfaces with single-residue resolution. We revealed that the interaction between 14-3-3 and Tau proteins is mediated not only via the 14-3-3 amphipathic binding grooves, but also via less specific interactions with 14-3-3 protein surface and, in the case of monomeric 14-3-3, also partially via the exposed dimeric interface. In addition, the hyperphosphorylation of Tau changes its affinity to 14-3-3 proteins. In conclusion, we propose quite complex interaction mode between the Tau and 14-3-3 proteins.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info