Transiently Misacylated tRNA Is a Primer for Editing of Misactivated Adenylates by Class I Aminoacyl-tRNA Synthetases

详细信息    查看全文

• 作者：Brian E. Nordin and Paul Schimmel
• 刊名：Biochemistry
• 出版年：2003
• 出版时间：November 11, 2003
• 年：2003
• 卷：42
• 期：44
• 页码：12989 - 12997
• 全文大小：213K
• 年卷期：v.42,no.44(November 11, 2003)
• ISSN：1520-4995

文摘

The genetic code depends on amino acid fine structure discrimination by aminoacyl-tRNAsynthetases. For isoleucyl- (IleRS) and valyl-tRNA synthetases (ValRS), reactions that hydrolyze misactivated noncognate amino acids help to achieve high accuracy in aminoacylation. Two editing pathwayscontribute to aminoacylation fidelity: pretransfer and post-transfer. In pretransfer editing, the misactivatedamino acid is hydrolyzed as an aminoacyl adenylate, while in post-transfer editing a misacylated tRNAis deacylated. Both reactions are dependent on a tRNA cofactor and require translocation to a site located~30 Å from the site of amino acid activation. Using a series of 3'-end modified tRNAs that are deficientin either aminoacylation, deacylation, or both, total editing (the sum of pre- and post-transfer editing)was shown to require both aminoacylation and deacylation activities. These and additional results withIleRS are consistent with a post-transfer deacylation event initiating formation of an editing-active enzyme/tRNA complex. In this state, the primed complex processively edits misactivated valyl-adenylate via thepretransfer route. Thus, misacylated tRNA is an obligatory intermediate for editing by either pathway.