生物谷报道：美国科学家的一项最新研究表明，一种远古真菌的分子晶体结构可以作为“时间机器”，向人们展示生命从简单向复杂进化的重要一环——蛋白质如何进化出功能。相关论文发表在1月3日的《自然》杂志上。
进行该项研究的是美国普渡大学和德克萨斯大学的科学家。通过研究该真菌与RNA绑定的蛋白三维结构，研究人员对生命如何从早期的自我复制分子进化为让蛋白质分担一些功能有了直观的认识。德克萨斯大学细胞与分子生物学研究所主任Alan Lambowitz说，“现在我们知道RNA怎样逐渐与蛋白质进行功能分工了，这是重要的‘缺失的一环’。”
普渡大学的结构生物学家Barbara Golden表示，“人们通常认为RNA或者类似的分子存在于最早的生命分子当中，它们既携带遗传编码，同时也要折叠成各种结构，从而能够在细胞内工作。曾几何时，RNA发生进化，能够产生蛋白质，而就是这时，蛋白质也开始协助并逐渐接过许多此前RNA承担的功能角色——作为催化剂和细胞内的建筑结构，生命也变得越来越复杂。”
为了弄清这一关键过程的细节，Lambowitz、Golden和论文第一作者Paul Paukstelis等人利用分子结晶技术，看清了这种远古真菌蛋白的晶体结构，并推断其如何工作。这让研究人员明确了两个问题，一是该蛋白利用两种截然不同的分子外表来实现两种功能；二是该蛋白完成的工作与其他简单生物中RNA完成的工作十分相似。
新的发现除了科学本身的意义，还有重要的应用价值。Lambowitz说，“该成果有望应用于抗真菌药物的研发，抵御致死性病原体。此外，如果能创造出更多的结构，科学家将会对远古生物体内化学反应有更深入的理解。”
生物谷推荐原始出处：
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).
Abstract
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.
