小柯机器人

科学家阐明tRNA校正过程
2020-07-04 16:14

美国马萨诸塞大学医学院Andrei A. Korostelev研究组取得最新进展。他们解析了包含EF-Tu•GTP组分的延伸核糖体冷冻电镜结构,从而阐明了tRNA的校正过程。相关论文发表在2020年7月1日出版的《自然》杂志上。

他们使用时间分辨冷冻电镜来揭示了EF-Tu•GTP传递氨酰基-tRNA后的33种核糖体状态。核糖体解码中心不是在初始识别时锁定相关的tRNA,而是动态监控GTP水解前后的密码子-反密码子相互作用。GTP水解使EF-Tu的GTPase结构域延伸开,从tRNA释放EF-Tu。然后,30S亚基将相关的tRNA锁定在解码中心并旋转,从而使tRNA在适应肽基转移酶中心的过程中绕过50S突起。

相比之下,解码中心无法锁定近同源的tRNA,从而在初始选择(GTP水解之前)和校对(GTP水解之后)期间都可以解离近同源的tRNA。这些发现揭示了在初始选择状态和校对状态下核糖体之间的结构相似性,这两个状态共同控制了错误tRNA的有效排斥。

研究人员表示,核糖体通过校对延伸因子EF-Tu传递的每个氨酰基tRNA来准确地解码mRNA。要了解此校对步骤的分子机制需要可视化GTP催化的延伸过程,但这仍然是一个挑战。

附:英文原文

Title: Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading

Author: Anna B. Loveland, Gabriel Demo, Andrei A. Korostelev

Issue&Volume: 2020-07-01

Abstract: Ribosomes accurately decode mRNA by proofreading each aminoacyl-tRNA that is delivered by the elongation factor EF-Tu1. To understand the molecular mechanism of this proofreading step it is necessary to visualize GTP-catalysed elongation, which has remained a challenge2,3,4. Here we use time-resolved cryogenic electron microscopy to reveal 33 ribosomal states after the delivery of aminoacyl-tRNA by EF-TuGTP. Instead of locking cognate tRNA upon initial recognition, the ribosomal decoding centre dynamically monitors codon–anticodon interactions before and after GTP hydrolysis. GTP hydrolysis enables the GTPase domain of EF-Tu to extend away, releasing EF-Tu from tRNA. The 30S subunit then locks cognate tRNA in the decoding centre and rotates, enabling the tRNA to bypass 50S protrusions during accommodation into the peptidyl transferase centre. By contrast, the decoding centre fails to lock near-cognate tRNA, enabling the dissociation of near-cognate tRNA both during initial selection (before GTP hydrolysis) and proofreading (after GTP hydrolysis). These findings reveal structural similarity between ribosomes in initial selection states5,6 and in proofreading states, which together govern the efficient rejection of incorrect tRNA.

DOI: 10.1038/s41586-020-2447-x

Source: https://www.nature.com/articles/s41586-020-2447-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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