Přehled o publikaci
2023
14-3-3 dimer vs monomer – (dis)similarities in Tau protein binding
KOZELEKOVÁ, Aneta, Lucia IĽKOVIČOVÁ, Radek CRHA, Alena HOFROVÁ, Jozef HRITZ et. al.Basic information
Original name
14-3-3 dimer vs monomer – (dis)similarities in Tau protein binding
Name in Czech
14-3-3 dimer vs monomer – (ne)podobnost ve vazbě proteinu Tau
Authors
KOZELEKOVÁ, Aneta, Lucia IĽKOVIČOVÁ, Radek CRHA, Alena HOFROVÁ and Jozef HRITZ
Edition
EBSA Congress 2023 in Stockholm, 2023
Other information
Language
English
Type of outcome
Konferenční abstrakta
Confidentiality degree
is not subject to a state or trade secret
References:
Organization
Středoevropský technologický institut – Repository – Repository
Keywords in English
Neurofibrillary tangles; Tau protein; brain; NMR; affinity
Links
GF20-05789L, research and development project. MUNI/A/1413/2022, research and development project. 101087124, research and development project.
Changed: 7/3/2024 03:59, RNDr. Daniel Jakubík
Abstract
V originále
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.
