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@proceedings{60028,
author = {Kozeleková, Aneta and Iľkovičová, Lucia and Crha, Radek and Hofrová, Alena and Hritz, Jozef},
booktitle = {EBSA Congress 2023 in Stockholm},
doi = {http://dx.doi.org/10.1007/s00249-023-01668-7},
keywords = {Neurofibrillary tangles; Tau protein; brain; NMR; affinity},
language = {eng},
title = {14-3-3 dimer vs monomer – (dis)similarities in Tau protein binding},
url = {https://link.springer.com/article/10.1007/s00249-023-01668-7#preview},
year = {2023}
}
TY - CONF
ID - 60028
AU - Kozeleková, Aneta - Iľkovičová, Lucia - Crha, Radek - Hofrová, Alena - Hritz, Jozef
PY - 2023
TI - 14-3-3 dimer vs monomer – (dis)similarities in Tau protein binding
KW - Neurofibrillary tangles
KW - Tau protein
KW - brain
KW - NMR
KW - affinity
UR - https://link.springer.com/article/10.1007/s00249-023-01668-7#preview
N2 - Neurofibrillary tangles (NFTs), composed of aggregated hyperphosphorylated Tau protein, are one of the hallmarks of Alzheimer’s disease (AD). Up to now, the mechanism of Tau aggregation is not well understood. In the late 1990’s, 14-3-3 proteins, highly abundant proteins in brain, were found in NFTs. 14-3-3s usually exist as dimers, but after Ser58 phosphorylation they monomerize. In our project, we aimed to characterize the interaction between dimeric and monomeric 14-3-3s and PKA phosphorylated Tau (pTau). The binding affinity, stoichiometry and interacting residues were studied using native-PAGE, NMR spectroscopy, cross-linking and tandem MS. 14-3-3 dimer interacted with pTau with higher affinity and different stoichiometry compared to 14-3-3 monomer. Using NMR, interaction dissociation constants (KDs) of individual PKA phospho-sites on pTau were determined. Tau bound to 14-3-3 predominantly by microtubule binding domain, which suggests competition between 14-3-3s and microtubules in Tau binding and relation to AD pathology. In conclusion, we provide an insight into numerous aspects of binding between monomeric and dimeric 14 3-3s and Tau protein.
ER -
KOZELEKOVÁ, Aneta, Lucia IĽKOVIČOVÁ, Radek CRHA, Alena HOFROVÁ and Jozef HRITZ. 14-3-3 dimer vs monomer – (dis)similarities in Tau protein binding. In \textit{EBSA Congress 2023 in Stockholm}. 2023. Available from: https://dx.doi.org/10.1007/s00249-023-01668-7.
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