生物谷報道：美國科學家的一項最新研究表明,，一種遠古真菌的分子晶體結(jié)構可以作為“時間機器”,，向人們展示生命從簡單向復雜進化的重要一環(huán)——蛋白質(zhì)如何進化出功能。相關論文發(fā)表在1月3日的《自然》雜志上,。
進行該項研究的是美國普渡大學和德克薩斯大學的科學家。通過研究該真菌與RNA綁定的蛋白三維結(jié)構，研究人員對生命如何從早期的自我復制分子進化為讓蛋白質(zhì)分擔一些功能有了直觀的認識,。德克薩斯大學細胞與分子生物學研究所主任Alan Lambowitz說，“現(xiàn)在我們知道RNA怎樣逐漸與蛋白質(zhì)進行功能分工了，這是重要的‘缺失的一環(huán)’,。”
普渡大學的結(jié)構生物學家Barbara Golden表示,，“人們通常認為RNA或者類似的分子存在于最早的生命分子當中，它們既攜帶遺傳編碼,，同時也要折疊成各種結(jié)構,，從而能夠在細胞內(nèi)工作。曾幾何時,，RNA發(fā)生進化,，能夠產(chǎn)生蛋白質(zhì)，而就是這時,，蛋白質(zhì)也開始協(xié)助并逐漸接過許多此前RNA承擔的功能角色——作為催化劑和細胞內(nèi)的建筑結(jié)構,，生命也變得越來越復雜。”
為了弄清這一關鍵過程的細節(jié),，Lambowitz,、Golden和論文第一作者Paul Paukstelis等人利用分子結(jié)晶技術，看清了這種遠古真菌蛋白的晶體結(jié)構,，并推斷其如何工作,。這讓研究人員明確了兩個問題，一是該蛋白利用兩種截然不同的分子外表來實現(xiàn)兩種功能,；二是該蛋白完成的工作與其他簡單生物中RNA完成的工作十分相似,。
新的發(fā)現(xiàn)除了科學本身的意義，還有重要的應用價值,。Lambowitz說,，“該成果有望應用于抗真菌藥物的研發(fā)，抵御致死性病原體,。此外,，如果能創(chuàng)造出更多的結(jié)構，科學家將會對遠古生物體內(nèi)化學反應有更深入的理解,。”
生物谷推薦原始出處：
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: [email protected]) or B.L.G. (Email: [email protected]).
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.
