Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III
Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III
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DOI：
10.1016/j.cell.2005.11.034
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发表时间：
2006-01-27
期刊：
影响因子：
64.5
通讯作者：
Ji, XH
中科院分区：
文献类型：
--
作者：
Gan, JH;Tropea, JE;Ji, XH
核糖核酸酶III（RNase III）家族的成员是双链RNA（dsRNA）特定的内切核核酸酶，其活性中心的特征为具有签名基序和其产品中的两个基准3'Over-unthang。尽管DICER产生了小型干扰RNA，但目前是强烈感兴趣的重点，但结构上更简单的细菌RNase III是整个家庭的范式。在这里，我们介绍了RNase III-Lododuct络合物的晶体结构，这是该家族观察到的第一个催化复合物。蛋白质中的7个残基接头促进了蛋白-RNA识别的诱导拟合。蛋白RNA相互作用的模式，由RNase III中的四个RNA结合基序定义，DSRNA中的三个蛋白质相互作用盒是负责底物特异性的，而保守的氨基酸残基和分离的阳离子负责scissile-bond-Bond-Bond-Bond-Bond裂解。该结构揭示了有关RNA水解机制的大量信息，这些信息可以推断到其他RNase III家族成员。
Members of the ribonuclease III (RNase III) family are double-stranded RNA (dsRNA) specific endoribonucleases characterized by a signature motif in their active centers and a two-base 3' overhang in their products. While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family. Here, we present the crystal structure of an RNase III-product complex, the first catalytic complex observed for the family. A 7 residue linker within the protein facilitates induced fit in protein-RNA recognition. A pattern of protein-RNA interactions, defined by four RNA binding motifs in RNase III and three protein-interacting boxes in dsRNA, is responsible for substrate specificity, while conserved amino acid residues and divalent cations are responsible for scissile-bond cleavage. The structure reveals a wealth of information about the mechanism of RNA hydrolysis that can be extrapolated to other RNase III family members.