Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade.
Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade.
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DOI：
10.7554/elife.27826
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发表时间：
2017-08-15
期刊：
影响因子：
7.7
通讯作者：
van der Goot FG
中科院分区：
文献类型：
--
作者：
Abrami L;Dallavilla T;Sandoz PA;Demir M;Kunz B;Savoglidis G;Hatzimanikatis V;van der Goot FG
S-棕榈酰化是唯一可逆的翻译后脂质修饰。关于DHHC棕榈酰转移酶家族的知识仍然有限。在这里，我们证明了人的ZDHHC6，它修改内质网的关键蛋白，由上游棕榈酰转移酶ZDHHC16控制，揭示了第一个棕榈酰化级联反应。结合三个ZDHHC6棕榈酰化位点的定点突变、动力学参数的实验测定和数据驱动的数学模型，我们可以获得关于八个不同棕榈酰化ZDHHC6物种的详细信息。我们发现，物种通过ZDHHC16和酰基蛋白质硫代酯酶APT2的作用快速相互转换，每个物种的周转速度和活性都不同，总共允许细胞强有力地调节其ZDHHC6的活性。
S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species. We found that species rapidly interconvert through the action of ZDHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its ZDHHC6 activity.