Nature：线粒体tRNA合成酶与核酶复合体的晶体结构

生物谷

生物谷报道：地球上的生命据信是从一个“RNA世界”演化来的，在这个世界上，RNA分子既催化重要的化学反应，又携带遗传信息。在现代生物学中，蛋白已经成为细胞中完成酶催化作用的主要角色，而核酸则仍旧扮演携带遗传信息的角色。然而，在细胞内，仍然有RNA世界的遗迹。其中一个遗迹就是线粒体tyrosyl-tRNA合成酶CYT-18，它来自真菌链孢霉，也与一种group I intron核酶结合，并且帮助进行剪接。现在，这一蛋白/核酶复合体的晶体结构已被确定。它们的相互作用界面与CYT-18用来在其酶催化作用中与tRNATyr结合的界面是不同的。研究人员还发现了在非拼接tRNA合成酶中不存在的特定变化，它们可能是RNA-蛋白复合体从只有RNA的酶演化而来的方式。

生物谷推荐英文原文：

Nature 451, 94-97 (3 January 2008) | doi:10.1038/nature06413; Received 26 September 2007; Accepted 24 October 2007

Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA

Paul J. Paukstelis1, Jui-Hui Chen2, Elaine Chase2, Alan M. Lambowitz1,3 & Barbara L. Golden2,3

Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, and Section of Molecular Genetics and Microbiology, School of Biological Sciences, University of Texas at Austin, Austin, Texas 78712, USA
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907, USA
These authors contributed equally to this work.

Correspondence to: Alan M. Lambowitz1,3Barbara L. Golden2,3 Correspondence and requests for materials should be addressed to A.M.L. (Email: lambowitz@mail.utexas.edu) or B.L.G. (Email: barbgolden@purdue.edu).

The 'RNA world' hypothesis holds that during evolution the structural and enzymatic functions initially served by RNA were assumed by proteins, leading to the latter's domination of biological catalysis. This progression can still be seen in modern biology, where ribozymes, such as the ribosome and RNase P, have evolved into protein-dependent RNA catalysts ('RNPzymes'). Similarly, group I introns use RNA-catalysed splicing reactions, but many function as RNPzymes bound to proteins that stabilize their catalytically active RNA structure1, 2. One such protein, the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (TyrRS; CYT-18), is bifunctional and both aminoacylates mitochondrial tRNATyr and promotes the splicing of mitochondrial group I introns3. Here we determine a 4.5-Å co-crystal structure of the Twort orf142-I2 group I intron ribozyme bound to splicing-active, carboxy-terminally truncated CYT-18. The structure shows that the group I intron binds across the two subunits of the homodimeric protein with a newly evolved RNA-binding surface distinct from that which binds tRNATyr. This RNA binding surface provides an extended scaffold for the phosphodiester backbone of the conserved catalytic core of the intron RNA, allowing the protein to promote the splicing of a wide variety of group I introns. The group I intron-binding surface includes three small insertions and additional structural adaptations relative to non-splicing bacterial TyrRSs, indicating a multistep adaptation for splicing function. The co-crystal structure provides insight into how CYT-18 promotes group I intron splicing, how it evolved to have this function, and how proteins could have incrementally replaced RNA structures during the transition from an RNA world to an RNP world.