纪念斯隆-凯特琳癌肿中心科学家解析了困扰人们数十年的Argonaute蛋白质的晶体结构。Argonaute蛋白质是RNAi干扰(RNA interference，RNAi)通路中起关键作用的复合合物，这一结构的解析为蛋白的运作提供了重要的实验依据,为阐释RNAi沉默过程等深入研究提供了有力的支持。这一研究成果发表在Nature杂志上。
RNAi干扰)过程非常复杂, 其中Argonaute蛋白参与的加工过程是最为重要的环节之一。Argonaute复合体通过识别被Dicer酶酶切的dsRNA碎片，裂解双链RNA中一条链，从而防止它作为蛋白生产的模板，而后另一条RNA行使干扰功能。研究者通过一系列的测定解析蛋白结构，发现Argonaute蛋白是一个具有复杂拓扑结构和多个活动元件的大分子蛋白，通过掺入少量RNA转变成一种含4元件活化部位的激活态。这一发现为RNA干扰过程的研究提供又一个可靠的依据，为今后开展RNAi在人类疾病的治疗等各方面的研究提供更广阔的应用前景。
Structure of yeast Argonaute with guide RNA
Nature. 2012 Jun 20;486(7403):368-74. doi: 10.1038/nature11211.
Abstract:The RNA-induced silencing complex, comprising Argonaute and guide RNA, mediates RNA interference. Here we report the 3.2 Å crystal structure of Kluyveromyces polysporus Argonaute (KpAGO) fortuitously complexed with guide RNA originating from small-RNA duplexes autonomously loaded by recombinant KpAGO. Despite their diverse sequences, guide-RNA nucleotides 1-8 are positioned similarly, with sequence-independent contacts to bases, phosphates and 2'-hydroxyl groups pre-organizing the backbone of nucleotides 2-8 in a near-A-form conformation. Compared with prokaryotic Argonautes, KpAGO has numerous surface-exposed insertion segments, with a cluster of conserved insertions repositioning the N domain to enable full propagation of guide-target pairing. Compared with Argonautes in inactive conformations, KpAGO has a hydrogen-bond network that stabilizes an expanded and repositioned loop, which inserts an invariant glutamate into the catalytic pocket. Mutation analyses and analogies to ribonuclease H indicate that insertion of this glutamate finger completes a universally conserved catalytic tetrad, thereby activating Argonaute for RNA cleavage.