Nuclear Magnetic Resonance Analysis of the Acetylation Pattern of the Neuronal Tau Protein
Nuclear Magnetic Resonance Analysis of the Acetylation Pattern of the Neuronal Tau Protein
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DOI：
10.1021/bi500006v
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发表时间：
2014-05-13
期刊：
影响因子：
2.9
通讯作者：
Smet-Nocca, Caroline
中科院分区：
文献类型：
--
作者：
Kamah, Amina;Huvent, Isabelle;Smet-Nocca, Caroline
神经元Tau蛋白的赖氨酸乙酰化被描述为翻译后调节Tau功能的一种新机制，在与阿尔茨海默病相关的微管结合和聚集过程中具有重要结果。在这里，我们使用高分辨率核磁共振光谱，在每个残基的分辨率下，揭示了CREB结合蛋白(CBP)乙酰转移酶对全长Tau的乙酰化模式。我们的研究给出了CBP介导的乙酰化反应的定量概述，并检查了催化熟练程度，因为与乙酰辅酶A的非酶反应发生在体外。此外，我们还研究了乙酰化牛磺酸在肝素诱导的聚集实验中对牛磺酸纤化的影响以及对肝素结合的影响。
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.