2012年5月24日,，美國(guó)冷泉港實(shí)驗(yàn)室結(jié)構(gòu)生物學(xué)家Leemor Joshua-Tor等報(bào)道了hAgo2（human Argonaute-2）與miR-20a( microRNA-20a )復(fù)合體高分辨率的晶體結(jié)構(gòu),，該研究成果發(fā)表在最新一期的Cell上,。
AGO蛋白（Argonaute proteins）是RNA引導(dǎo)的沉默復(fù)合體（RNA-Induced Silencing Complex ，RISC）的核心元件,，用于引導(dǎo)小RNA識(shí)別靶標(biāo),。原核AGO 蛋白(argonaute proteins) 由N 末端,，PAZ,，MID 和PIWI4個(gè)結(jié)構(gòu)域組成,。
研究發(fā)現(xiàn)，人AGO蛋白的總體結(jié)構(gòu)與結(jié)構(gòu)域組成與原核AGO蛋白基本一致,。還發(fā)現(xiàn),，miRNA錨定在mid和PAZ結(jié)構(gòu)域末端，在結(jié)合槽（binding groove)形成k-turn ,。
更加有趣的是，miRNA的結(jié)合顯著提高了hAgo2的穩(wěn)定性,，使其能保持穩(wěn)定的蛋白構(gòu)象,。
此研究為理解Ago2在發(fā)育和疾病發(fā)生中的功能提供了框架。(生物谷Bioon.com）
doi:10.1016/j.cell.2012.05.017
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PMID:
The Structure of Human Argonaute-2 in Complex with miR-20a
Elad Elkayam,，Claus-D. Kuhn,，Ante Tocilj，Astrid D. Haase,，Emily M. Greene,，Gregory J.Hannon，and Leemor Joshua-Tor
Argonaute proteins lie at the heart of the RNA-Induced Silencing Complex (RISC),， wherein they use small RNA guides to recognize targets. Prior studies established the architecture of Argonaute proteins and revealed a crescent-shaped base made up of the amino-terminal,， PAZ，middle,and PIWI domains,； however,， these studies were based on prokaryotic Argonaute proteins of unclearbiochemical and biological function. Here we report the crystal structure of human Argonaute-2 bound to microRNA-20a at 2.2 ？ resolution. Overall architecture and domain organization is shared with its prokaryotic counterparts,， although hAgo2′s PAZ domain is further removed from other domains. The miRNA is anchored at both ends by the mid- and PAZ domains but makes several kinks and turns along the binding groove. Interestingly,， miRNA binding confers remarkable stability on hAgo2， locking this otherwise flexible enzyme into a stable conformation. Our findings provide a framework to understand the functions of Ago2 in essential processes in development and disease.
