Details

Autor(en) / Beteiligte

• Despres, Clément
• Byrne, Cillian
• Qi, Haoling
• Cantrelle, François-Xavier
• Huvent, Isabelle
• Chambraud, Béatrice
• Baulieu, Etienne-Emile
• Jacquot, Yves
• Landrieu, Isabelle
• Lippens, Guy
• Smet-Nocca, Caroline

Titel

Identification of the Tau phosphorylation pattern that drives its aggregation

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-08, Vol.114 (34), p.9080-9085

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Determining the functional relationship between Tau phosphorylation and aggregation has proven a challenge owing to the multiple potential phosphorylation sites and their clustering in the Tau sequence. We use here in vitro kinase assays combined with NMR spectroscopy as an analytical tool to generate well-characterized phosphorylated Tau samples and show that the combined phosphorylation at the Ser202/Thr205/Ser208 sites, together with absence of phosphorylation at the Ser262 site, yields a Tau sample that readily forms fibers, as observed by thioflavin T fluorescence and electron microscopy. On the basis of conformational analysis of synthetic phosphorylated peptides, we show that aggregation of the samples correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205.