Počet záznamů: 1
Phosphorylated full-length Tau interacts with 14-3-3 proteins via two short phosphorylated sequences, each occupying a binding groove of 14-3-3 dimer
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SYSNO ASEP 0541623 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Phosphorylated full-length Tau interacts with 14-3-3 proteins via two short phosphorylated sequences, each occupying a binding groove of 14-3-3 dimer Tvůrce(i) Neves, J. F. (FR)
Petrvalská, Olivia (FGU-C) RID, ORCID, SAI
Bosica, F. (SE)
Cantrelle, F. X. (FR)
Merzougui, H. (FR)
O'Mahony, G. (SE)
Hanoulle, X. (FR)
Obšil, Tomáš (FGU-C) RID, ORCID
Landrieu, I. (FR)Zdroj.dok. FEBS Journal - ISSN 1742-464X
Roč. 288, č. 6 (2021), s. 1918-1934Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova 14‐3‐3 proteins ; Alzheimer’s disease ; analytical ultracentrifugation ; NMR spectroscopy ; protein–protein interactions ; Tau protein Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000579307500001 EID SCOPUS 85092269843 DOI 10.1111/febs.15574 Anotace Protein-protein interactions (PPIs) remain poorly explored targets for the treatment of Alzheimer's disease. The interaction of 14-3-3 proteins with Tau was shown to be linked to Tau pathology. This PPI is therefore seen as a potential target for Alzheimer's disease. When Tau is phosphorylated by PKA (Tau-PKA), several phosphorylation sites are generated, including two known 14-3-3 binding sites, surrounding the phosphorylated serines 214 and 324 of Tau. The crystal structures of 14-3-3 in complex with peptides surrounding these Tau phosphosites show that both these motifs are anchored in the amphipathic binding groove of 14-3-3. However, in the absence of structural data with the full-length Tau protein, the stoichiometry of the complex or the interface and affinity of the partners is still unclear. In this work, we addressed these points, using a broad range of biophysical techniques. The interaction of the long and disordered Tau-PKA protein with 14-3-3 sigma is restricted to two short sequences, containing phosphorylated serines, which bind in the amphipathic binding groove of 14-3-3 sigma. Phosphorylation of Tau is fundamental for the formation of this stable complex, and the affinity of the Tau-PKA/14-3-3 sigma interaction is in the 1-10 micromolar range. Each monomer of the 14-3-3 sigma dimer binds one of two different phosphorylated peptides of Tau-PKA, suggesting a 14-3-3/Tau-PKA stoichiometry of 2 : 1, confirmed by analytical ultracentrifugation. These results contribute to a better understanding of this PPI and provide useful insights for drug discovery projects aiming at the modulation of this interaction. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://doi.org/10.1111/febs.15574
Počet záznamů: 1