Evolutionary Divergence of Enzymatic Mechanisms for Posttranslational Polyglycylation
Evolutionary Divergence of Enzymatic Mechanisms for Posttranslational Polyglycylation
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DOI：
10.1016/j.cell.2009.05.020
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发表时间：
2009-06-12
期刊：
影响因子：
64.5
通讯作者：
Janke, Carsten
中科院分区：
文献类型：
--
作者：
Rogowski, Krzysztof;Juge, Francois;Janke, Carsten
聚甘氨酰化是一种翻译后修饰，在蛋白质上产生甘氨酸侧链。在这里，我们确定了一个家庭的进化保守的甘氨酸连接酶，修改微管蛋白使用不同的酶机制。在哺乳动物中，两种不同的酶类型催化多聚甘氨酰化的起始和延伸步骤，而果蝇甘氨酰化酶是双功能的。我们进一步表明，人类延长glycylase已经失去了酶活性，由于两个氨基酸的变化，这表明蛋白质的糖基化的功能，可以充分履行由monoglycylation。使用RNA干扰在果蝇中耗尽一种甘氨酰化酶，导致成年果蝇总甘氨酰化水平显著降低，雄性不育与精子个体化和轴丝维持缺陷相关。更严重的RNAi消耗在早期发育阶段是致命的，表明蛋白质甘氨酰化是必不可少的。连同观察到多种蛋白质被甘氨酰化，我们的功能数据指向甘氨酰化在蛋白质功能中的一般作用。
Polyglycylation is a posttranslational modification that generates glycine side chains on proteins. Here we identify a family of evolutionarily conserved glycine ligases that modify tubulin using different enzymatic mechanisms. In mammals, two distinct enzyme types catalyze the initiation and elongation steps of polyglycylation, whereas Drosophila glycylases are bifunctional. We further show that the human elongating glycylase has lost enzymatic activity due to two amino acid changes, suggesting that the functions of protein glycylation could be sufficiently fulfilled by monoglycylation. Depletion of a glycylase in Drosophila using RNA interference results in adult flies with strongly decreased total glycylation levels and male sterility associated with defects in sperm individualization and axonemal maintenance. A more severe RNAi depletion is lethal at early developmental stages, indicating that protein glycylation is essential. Together with the observation that multiple proteins are glycylated, our functional data point towards a general role of glycylation in protein functions.