2月7日,，發(fā)表了中科院上海生命科學院生化與細胞所王恩多研究組的最新研究成果：亮氨酰-tRNA合成酶具有不依賴tRNA的轉移前編校,。
氨基酰-tRNA合成酶(AARS)在體內(nèi)催化合成氨基酰-tRNA,，為蛋白質(zhì)生物合成提供原料,。通常,，該催化反應為兩步反應,，首先氨基酸被ATP活化,，生成反應中間體氨基酰-AMP,，然后被活化的氨基酸轉移到tRNA的3’末端，生成氨基酰-tRNA。該催化反應的精確性對遺傳信息的翻譯,、蛋白質(zhì)的功能甚至生物體生存至關重要,。一些AARS在漫長的進化過程中獲得編校功能來水解錯誤的中間體或錯誤的產(chǎn)物，以保證反應的精確性,、避免錯誤的氨基酸參入蛋白質(zhì),。AARS對錯誤氨基酸轉移到tRNA之前和之后的編校分別稱為轉移前和轉移后的編校。王恩多組2000年首次報道了亮氨酰-tRNA合成酶（LeuRS）具有發(fā)生在獨立編校結構域（CP1）的轉移后的編校,。是否LeuRS具有其它的編校途徑,？
王恩多組的朱斌，姚鵬和譚敏發(fā)現(xiàn)進化樹底部的超嗜熱菌 Aquifex aeolicus 的LeuRS (AaLeuRS) 具有不依賴tRNA的轉移前編?；盍?，可以直接水解被AaLeuRS誤活化的氨基酸。其活性中心不在CP1結構域,，而在氨基?；钚灾行模珹aLeuRS催化誤活化氨基酸的水解速度遠高于誤活化氨基酸自發(fā)水解的速度,。本篇工作的意義在于發(fā)現(xiàn)：LeuRS的氨基?；钚灾行某送ㄟ^氨基酸的分子大小來“粗篩”氨基酸底物以外，還具有對反應中間體的“細篩”功能,，進而揭示了AARS催化反應的精確性是多層次,、多結構域共同協(xié)同作用的結果。
該項目受到國家科技部,、國家基金委及上海市科委的經(jīng)費支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Biol. Chem., Vol. 284, Issue 6, 3418-3424, February 6, 2009
tRNA-independent Pretransfer Editing by Class I Leucyl-tRNA Synthetase*
Bin Zhu1, Peng Yao1, Min Tan1, Gilbert Eriani, and En-Duo Wang2
From the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China and the Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, Université Louis Pasteur, 15 Rue René Descartes, 67084 Strasbourg, France
Aminoacyl-tRNA synthetases catalyze the formation of aminoacyl-tRNA in a two-step reaction starting with amino acid activation followed by aminoacyl group transfer to tRNA. To clear mistakes that occasionally occur, some of these enzymes carry out editing activities, acting on the misactivated amino acid (pretransfer editing) or after the transfer on the tRNA (post-transfer editing). The post-transfer editing pathway of leucyl-tRNA synthetase has been extensively studied by structural and biochemical approaches. Here, we report the finding of a tRNA-independent pretransfer editing pathway in leucyl-tRNA synthetases from Aquifex aeolicus. Using a CP1-mutant defective in its post-transfer editing function, we showed that this new editing pathway is distinct from the post-transfer editing site and may occur at the synthetic catalytic site, as recently proposed for other aminoacyl-tRNA synthetases.
