A targeted multienzyme mechanism for selective microtubule polyglutamylation
A targeted multienzyme mechanism for selective microtubule polyglutamylation
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DOI：
10.1016/j.molcel.2007.04.012
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发表时间：
2007-05-11
期刊：
影响因子：
16
通讯作者：
Janke, Carsten
中科院分区：
文献类型：
--
作者：
van Dijk, Juliette;Rogowski, Krzysztof;Janke, Carsten
聚谷氨酸酶是在蛋白质上形成可变长度的聚谷氨酸侧链的酶。微管蛋白的多聚谷氨酰化被认为调节微管（MT）与MT相关蛋白和分子马达的相互作用。MT亚群是差异聚谷氨酰胺化的，但只有一个修饰酶已在哺乳动物中发现。为了更好地了解微管蛋白多聚谷氨酰化的异质性外观，我们寻找额外的酶，并在这里报告六种哺乳动物多聚谷氨酰化酶的鉴定。它们中的每一种都具有特征性的催化模式，并在MT上产生不同的修饰模式，这些模式可以通过多种酶的合作进一步多样化。多聚谷氨酰化酶通过差异表达和定位而局限于局限的组织和MT亚型。总之，我们提出了一个多酶，多聚谷氨酰化的机制，可以解释选择类型的MT的多聚谷氨酰化的多样性是如何控制在分子水平上。
Polyglutamylases are enzymes that form polyglutamate side chains of variable lengths on proteins. Polyglutamylation of tubulin is believed to regulate interactions of microtubules (MTs) with MT-associated proteins and molecular motors. Subpopulations of MTs are differentially polyglutamylated, yet only one modifying enzyme has been discovered in mammals. In an attempt to better understand the heterogeneous appearance of tubulin polyglutamylation, we searched for additional enzymes and report here the identification of six mammalian polyglutamylases. Each of them has a characteristic mode of catalysis and generates distinct patterns of modification on MTs, which can be further diversified by cooperation of multiple enzymes. Polyglutamylases are restricted to confined tissues and subtypes of MTs by differential expression and localization. In conclusion, we propose a multienzyme, mechanism of polyglutamylation that can explain how the diversity of polyglutamylation on selected types of MTs is controlled at the molecular level.