Regulation of One-Carbon Metabolism in Arabidopsis: The N-Terminal Regulatory Domain of Cystathionine γ-Synthase Is Cleaved in Response to Folate Starvation1[W]
Regulation of One-Carbon Metabolism in Arabidopsis: The N-Terminal Regulatory Domain of Cystathionine γ-Synthase Is Cleaved in Response to Folate Starvation1[W]
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DOI：
10.1104/pp.107.105379
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发表时间：
2007-08
期刊：
影响因子：
7.4
通讯作者：
Karen Loizeau;B. Gambonnet;Guo-Fang Zhang;G. Curien;Samuel Jabrin;D. Van Der Straeten;W. Lambert;F. Rébeillé;S. Ravanel
中科院分区：
文献类型：
--
作者：
Karen Loizeau;B. Gambonnet;Guo-Fang Zhang;G. Curien;Samuel Jabrin;D. Van Der Straeten;W. Lambert;F. Rébeillé;S. Ravanel
在所有生物体中，叶酸稳态的控制对于维持对一碳(C1)单位的需求至关重要，而一碳单位在主要代谢途径中是必不可少的。在这项研究中，我们用两种抗叶酸抑制剂诱导拟南芥细胞叶酸缺乏。这种处理引发了叶酸库的迅速而重要的减少，并显著改变了C1取代的叶酸辅酶的分布，这表明一种适应性反应有利于C1单元的通量优先于蛋氨酸(Met)的合成而不是核苷酸的合成。叶酸缺乏细胞的代谢图谱表明，由于缺乏底物5-甲基-四氢叶酸的蛋氨酸合成酶的损伤，激活的甲基循环受到了重要的干扰。有趣的是，S-腺苷-蛋氨酸和蛋氨酸库在叶酸饥饿的最初阶段有所下降，但进一步恢复到典型水平。蛋氨酸和S-腺苷-蛋氨酸的动态平衡是伴随着一个未知的翻译后修饰而来的，该修饰包括去除第一个蛋氨酸合成特异性酶--胱硫醚γ-合成酶N末端的92个氨基酸。抢救实验和对不同应力的分析表明，CGS处理与叶酸库的扰动特别相关。此外，CGS加工涉及在叶酸饥饿的各种植物中表达的氯塑性丝氨酸型蛋白水解酶。我们认为，到目前为止尚未确定的代谢效应器可以通过与酶的N-末端结构域相互作用来调节体内CGS的活性，而去除这个结构域可以抑制这种调节。
In all organisms, control of folate homeostasis is of vital importance to sustain the demand for one-carbon (C1) units that are essential in major metabolic pathways. In this study we induced folate deficiency in Arabidopsis (Arabidopsis thaliana) cells by using two antifolate inhibitors. This treatment triggered a rapid and important decrease in the pool of folates with significant modification in the distribution of C1-substituted folate coenzymes, suggesting an adaptive response to favor a preferential shuttling of the flux of C1 units to the synthesis of nucleotides over the synthesis of methionine (Met). Metabolic profiling of folate-deficient cells indicated important perturbation of the activated methyl cycle because of the impairment of Met synthases that are deprived of their substrate 5-methyl-tetrahydrofolate. Intriguingly, S-adenosyl-Met and Met pools declined during the initial period of folate starvation but were further restored to typical levels. Reestablishment of Met and S-adenosyl-Met homeostasis was concomitant with a previously unknown posttranslational modification that consists in the removal of 92 amino acids at the N terminus of cystathionine γ-synthase (CGS), the first specific enzyme for Met synthesis. Rescue experiments and analysis of different stresses indicated that CGS processing is specifically associated with perturbation of the folates pool. Also, CGS processing involves chloroplastic serine-type proteases that are expressed in various plant species subjected to folate starvation. We suggest that a metabolic effector, to date unidentified, can modulate CGS activity in vivo through an interaction with the N-terminal domain of the enzyme and that removal of this domain can suppress this regulation.