Nuclear magnetic resonance analysis of the acetylation pattern of the neuronal Tau protein.
Lysine acetylation of the neuronal Tau protein was described as a novel mechanism of posttranslational regulation of Tau functions with important outcomes in microtubule binding and aggregation processes related to Alzheimer's disease. Here, we unravel at a per-residue resolution the acetylation pattern of full-length Tau by the Creb-binding protein (CBP) acetyltransferase using high-resolution nuclear magnetic resonance spectroscopy. Our study gives a quantitative overview of CBP-mediated acetylation and examines the catalytic proficiency because the nonenzymatic reaction with acetyl-coenzyme A occurs in vitro. Furthermore, we have investigated with this characterized acetylated Tau the effect of acetylation on Tau fibrillization in a heparin-induced aggregation assay and on heparin binding.
Université de Lille-Nord de France, CNRS UMR 8576 , Institut Fédératif de Recherches 147, Villeneuve d'Ascq, France.
Amina
A
Kamah
Isabelle
I
Huvent
François-Xavier
FX
Cantrelle
Haoling
H
Qi
Guy
G
Lippens
Isabelle
I
Landrieu
Caroline
C
Smet-Nocca
D000107:Acetylation; D003545:Cysteine / Q000737:chemistry; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D011499:Protein Processing, Post-Translational; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D009587:Nitrogen Isotopes; D016875:tau Proteins; D006493:Heparin; D050880:p300-CBP Transcription Factors; D003545:Cysteine