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.
abstract: 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 V(364)PGF(367) 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.
authors.affiliation: Sorbonne Universités , UPMC Univ Paris 06, Ecole Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, 4, place Jussieu, 75252 Paris Cedex 05, France.|Institut Baulieu , INSERM UMR 1195, Neuroprotection and Neuroregeneration, Université Paris-Saclay, Bât. Gregory Pincus, 80, rue du Général Leclerc, 94276 Le Kremlin Bicêtre Cedex, France.
authors.forename: Cillian
authors.initials: C
authors.lastname: Byrne
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Morkos A
authors.initials: MA
authors.lastname: Henen
authors.affiliation: Sorbonne Universités , UPMC Univ Paris 06, Ecole Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, 4, place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Belnou
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Cantrelle
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Amina
authors.initials: A
authors.lastname: Kamah
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Haoling
authors.initials: H
authors.lastname: Qi
authors.affiliation: Institut Baulieu , INSERM UMR 1195, Neuroprotection and Neuroregeneration, Université Paris-Saclay, Bât. Gregory Pincus, 80, rue du Général Leclerc, 94276 Le Kremlin Bicêtre Cedex, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Giustiniani
authors.affiliation: Institut Baulieu , INSERM UMR 1195, Neuroprotection and Neuroregeneration, Université Paris-Saclay, Bât. Gregory Pincus, 80, rue du Général Leclerc, 94276 Le Kremlin Bicêtre Cedex, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Chambraud
authors.affiliation: Institut Baulieu , INSERM UMR 1195, Neuroprotection and Neuroregeneration, Université Paris-Saclay, Bât. Gregory Pincus, 80, rue du Général Leclerc, 94276 Le Kremlin Bicêtre Cedex, France.
authors.forename: Etienne-Emile
authors.initials: EE
authors.lastname: Baulieu
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.|LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.affiliation: CNRS, UMR 8576, Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.affiliation: Sorbonne Universités , UPMC Univ Paris 06, Ecole Normale Supérieure, PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, 4, place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D019696:Peptidylprolyl Isomerase