The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes
The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes
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DOI：
10.1038/nsb1016
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发表时间：
2003-12-01
期刊：
影响因子：
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通讯作者：
Joshua-Tor, L
中科院分区：
文献类型：
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作者：
Song, JJ;Liu, JD;Joshua-Tor, L
RISC是RNA诱导的沉默复合物，使用短干扰RNA（siRNA）或微小RNA（miRNA）以序列依赖性方式选择其靶点。RISC的关键组成部分是Argonaute蛋白，它包含两个特征结构域，PAZ和PIWI。PAZ是高度保守的，仅在Argonaute蛋白和Dicer中发现。我们已经解决了果蝇Argonaute2的PAZ结构域的晶体结构。PAZ结构域包含OB折叠的变体，OB折叠是通常结合单链核酸的模块。PAZ结构域显示低亲和力的核酸结合，可能与RNA单链区域的3个末端相互作用。PAZ可以结合siRNA的特征性两碱基3突出端，表明尽管PAZ可能不是Dicer或RISC中的主要核酸结合位点，但它可能有助于siRNA和miRNA特异性和有效地掺入RNAi途径。
RISC, the RNA-induced silencing complex, uses short interfering RNAs (siRNAs) or micro RNAs (miRNAs) to select its targets in a sequence-dependent manner. Key RISC components are Argonaute proteins, which contain two characteristic domains, PAZ and PIWI. PAZ is highly conserved and is found only in Argonaute proteins and Dicer. We have solved the crystal structure of the PAZ domain of Drosophila Argonaute2. The PAZ domain contains a variant of the OB fold, a module that often binds single-stranded nucleic acids. PAZ domains show low-affinity nucleic acid binding, probably interacting with the 3 ends of single-stranded regions of RNA. PAZ can bind the characteristic two-base 3 overhangs of siRNAs, indicating that although PAZ may not be a primary nucleic acid binding site in Dicer or RISC, it may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway.