Details

Autor(en) / Beteiligte

• Kamah, A.
• Cantrelle, F.X.
• Huvent, I.
• Giustiniani, J.
• Guillemeau, K.
• Byrne, C.
• Jacquot, Y.
• Landrieu, I.
• Baulieu, E.E.
• Smet, C.
• Chambraud, B.
• Lippens, G.

Titel

Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes

Ist Teil von

• Journal of molecular biology, 2016-03, Vol.428 (6), p.1080-1090

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •FKBP52 can isomerize selected prolyl bonds in Tau through its first FK506 domain.•Its peptidyl-prolyl isomerase activity is not linked to its capacity to oligomerize Tau.•A novel molecular interaction between the Tau PHF6 peptide and the two first domains of FKBP52 is characterized.•This physical interaction could stabilize an aggregation-prone conformation of Tau.