Control of protein life-span by N-terminal methionine excision
Control of protein life-span by N-terminal methionine excision
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DOI：
10.1093/emboj/cdg007
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发表时间：
2003-01-02
期刊：
影响因子：
11.4
通讯作者：
Meinnel, T
中科院分区：
文献类型：
--
作者：
Giglione, C;Vallon, O;Meinnel, T
肽脱甲酰基酶（PDFs）是近年来在真核生物基因组中发现的一类重要的蛋白质合成酶，其N端甲硫氨酸切除（NME）是蛋白质合成的一个保守途径。本研究以拟南芥和莱茵衣藻叶绿体编码蛋白质为模型系统，旨在揭示NME在整个蛋白质组中的功能。拟南芥中PDF1B的破坏导致白化病表型，以及对PDF特异性抑制剂放线菌素的极端敏感性。相反，PDF1A的敲除系没有表现出明显的表型。放线菌素的存在显著降低了莱茵衣藻细胞中光系统II的活性。脉冲追逐实验表明，PDF抑制导致不稳定的叶绿体编码的光系统II组件在C.reinhardtii的一个重要的子集。同样的蛋白质在pdf1b中也不稳定。定点取代改变最敏感的靶标亚基D2的NME，产生类似的效果。因此，质体NME是一个关键的机制，具体影响光系统II多肽的寿命。建议NME在调节蛋白质的关键子集的半衰期中的一般作用。
Peptide deformylases (PDFs) have been discovered recently in eukaryotic genomes, and it appears that N-terminal methionine excision (NME) is a conserved pathway in all compartments where protein synthesis occurs. This work aimed at uncovering the function(s) of NME in a whole proteome, using the chloroplast-encoded proteins of both Arabidopsis thaliana and Chlamydomonas reinhardtii as model systems. Disruption of PDF1B in A.thaliana led to an albino phenotype, and an extreme sensitivity to the PDF-specific inhibitor actinonin. In contrast, a knockout line for PDF1A exhibited no apparent phenotype. Photosystem II activity in C.reinhardtii cells was substantially reduced by the presence of actinonin. Pulse-chase experiments revealed that PDF inhibition leads to destabilization of a crucial subset of chloroplast-encoded photosystem II components in C.reinhardtii. The same proteins were destabilized in pdf1b. Site-directed substitutions altering NME of the most sensitive target, subunit D2, resulted in similar effects. Thus, plastid NME is a critical mechanism specifically influencing the life-span of photosystem II polypeptides. A general role of NME in modulating the half-life of key subsets of proteins is suggested.