Title :

A β-Turn Motif in the Steroid Hormone Receptor’s Ligand-Binding Domains Interacts with the Peptidyl-prolyl Isomerase (PPIase) Catalytic Site of the Immunophilin FKBP52

Author(s) :

Byrne, Cillian [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Laboratoire des biomolécules [LBM UMR 7203]
Henen, Morkos A. [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Belnou, Mathilde [Auteur]
Laboratoire des biomolécules [LBM UMR 7203]
Cantrelle, Francois-Xavier [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Kamah, Amina [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Qi, Haoling [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Giustiniani, Julien [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Chambraud, Béatrice [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Baulieu, Etienne-Emile [Auteur]
Petites Molécules de neuroprotection, neurorégénération et remyélinisation
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Landrieu, Isabelle [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Jacquot, Yves [Auteur]
Laboratoire des biomolécules [LBM UMR 7203]

Journal title :

Biochemistry

Volume number :

55

Pages :

5366-5376

Publication date :

2016-09-27

ISSN :

0006-2960, 1520-4995

HAL domain(s) :

Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire

English abstract : [en]

The immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor α (hERα) and using nuclear magnetic resonance, we show here that the short V364PGF367 ...
Show more >The immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor α (hERα) and using nuclear magnetic resonance, we show here that the short V364PGF367 sequence, which is located within its ligand-binding domain and adopts a type II β-turn conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif displays strong similarities with the FKBP52 FK1 domain-binding moiety of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin ligand with neuroprotective characteristics. An increase in the hydrophobicity of the residue preceding the proline and cyclization of the VPGF peptide strengthen its recognition by the FK1 domain of FKBP52. Replacement of the Pro residue with a dimethylproline also enhances this interaction. Our study not only contributes to a better understanding of how the interaction between the FK1 domain of FKBP52 and steroid hormone receptors most likely works but also opens new avenues for the synthesis of FKBP52 FK1 peptide ligands appropriate for the control of hormone-dependent physiological mechanisms or of the functioning of the Tau protein. Indeed, it has been shown that FKBP52 is involved in the intraneuronal dynamics of the Tau protein.Show less >

Language :

Anglais

Audience :

Non spécifiée

European Project :

Small molecule stabilizers of 14-3-3 Protein-Protein Interactions as novel drugs in cancer and neurodegenerative diseases

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

RMN et interactions moléculaires

Submission date :

2020-02-12T15:44:51Z
2021-02-25T15:24:17Z