title: Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes.
abstract: The aggregation of the neuronal Tau protein is one molecular hallmark of Alzheimer's disease and other related tauopathies, but the precise molecular mechanisms of the aggregation process remain unclear. The FK506 binding protein FKBP52 is able to induce oligomers in the pathogenic Tau P301L mutant and in a truncated form of the wild-type human Tau protein. Here, we investigate whether FKBP52's capacity to induce Tau oligomers depends on its prolyl cis/trans isomerase activity. We find that FKBP52 indeed can isomerize selected prolyl bonds in the different Tau proteins, and that this activity is carried solely by its first FK506 binding domain. Its capacity to oligomerize Tau is, however, not linked to this peptidyl-prolyl isomerase activity. In addition, we identified a novel molecular interaction implying the PHF6 peptide of Tau and the FK1/FK2 domains of FKBP52 independent of FK506 binding; these data point toward a non-catalytic molecular interaction that might govern the effect of FKBP52 on Tau.
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Kamah
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France.
authors.forename: F X
authors.initials: FX
authors.lastname: Cantrelle
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France.
authors.forename: I
authors.initials: I
authors.lastname: Huvent
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1195, Université Paris XI, Le Kremlin Bicêtre, France.
authors.forename: J
authors.initials: J
authors.lastname: Giustiniani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1195, Université Paris XI, Le Kremlin Bicêtre, France.
authors.forename: K
authors.initials: K
authors.lastname: Guillemeau
authors.affiliation: Sorbonne Universités, UPMC Univ Paris06, Ecole Normale Supérieure-PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, 4, Place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: C
authors.initials: C
authors.lastname: Byrne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris06, Ecole Normale Supérieure-PSL Research University, CNRS UMR 7203, Laboratoire des Biomolécules, 4, Place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Jacquot
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France.
authors.forename: I
authors.initials: I
authors.lastname: Landrieu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1195, Université Paris XI, Le Kremlin Bicêtre, France.
authors.forename: E E
authors.initials: EE
authors.lastname: Baulieu
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Smet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1195, Université Paris XI, Le Kremlin Bicêtre, France.
authors.forename: B
authors.initials: B
authors.lastname: Chambraud
authors.affiliation: University of Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, F 59 000 Lille, France; CNRS, INSA-Université Paul Sabatier, LISBP UMR5504, Toulouse, France. Electronic address: Guy.Lippens@insa-toulouse.fr.
authors.forename: G
authors.initials: G
authors.lastname: Lippens
mesh_terms: D006801:Humans; D007536:Isomerism; D066263:Protein Aggregation, Pathological; D055503:Protein Multimerization; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4
keywords: Alzheimer's disease; FKBP52; Tau; aggregation; prolyl cis/trans isomerase activity