生物谷报道:加州大学Santa Cruz分校的研究者确定了一种RNA酶或“核酶”的三维结构,它执行着合成新RNA分子所需的基础反应。他们的结果提供了探寻在数十亿年前生命出现的进化道路上出现的最早的自我复制分子的途径。
在目前所有已知的生命形式中,DNA和RNA分子的合成都是由蛋白质构成的酶完成。而合成这些蛋白的指令又包含在DNA或RNA(核酸)组成的基因中。这一循环的过程向生命起源理论提出了挑战。“谁先出现,是核酸还是蛋白质?这个问题似乎是个无法解决的悖论。但是随着核酶的发现,现在我们能构想出一个生物前的‘RNA世界’,其中自我复制的核酶同时完成了两项任务。”William Scott说,他是加州大学Santa Cruz分校的化学和生物化学副教授。
Scot和博士后研究员Michael Robertson确定了一种核酶的结构,它能将两个RNA的亚单位结合起来,这一反应与生物系统中称为RNA多聚酶的蛋白完成的反应相同。他们的发现发表在3月16日一期的《科学》杂志中。“RNA依赖的RNA多聚酶核酶是整个RNA世界假说的基础。” Robertson说,“通过它,你将能得到一个可以自我复制的RNA;在某些拷贝中出现的突变或错误导致的变异将受到达尔文自然选择的作用,这种分子就会进化成更大更好的核酶。这就是这一结构如此吸引人的原因。”Robertson和Scott确定结构的核酶并不是一个能完全自我复制的RNA分子,但是它的确能实现作为“连接酶”将两个RNA亚单位连接起来的基础反应。
Fig. 1. Ligation reaction and L1 ligase secondary structures. (A) Ligation reaction catalyzed by the L1 ligase in which the 3'-hydroxyl of the 3'-terminal residue of the substrate oligonucleotide attacks the -phosphorus of the ribozyme's 5'-terminal guanosine triphosphate, which creates a new phosphodiester bond. (B) The proposed secondary structure of the full-length L1 ribozyme. Nucleotides in lowercase are derived from the constant-sequence regions of the original N90 library; uppercase residues are derived from the randomized region of the pool. The substrate oligonucleotide is italicized. Positions within shaded boxes were invariant among clones isolated from a mutagenized reselection of the L1 ligase; positions in boldface were conserved in >85% of isolated clones. The dotted line indicates a base triple. [Figure adapted from (9).] (C) The secondary structure of the minimized crystallization construct, L1X6c
原文出处:
Science 16 March 2007 Vol 315, Issue 5818, Pages 1461-1610
The Structural Basis of Ribozyme-Catalyzed RNA Assembly
Michael P. Robertson and William G. Scott
Science 16 March 2007: 1549-1553.
A synthetic ribozyme catalyzes the bond formation necessary for RNA synthesis by transition-state stabilization and acid-base catalysis, perhaps as in an early RNA world.
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作者简介:
William Scott's home page and links