Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA
Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA
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DOI：
10.1016/j.cell.2016.09.002
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发表时间：
2016-10-06
期刊：
影响因子：
64.5
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Matsumoto, Naoki;Nishimasu, Hiroshi;Nureki, Osamu
PIWI进化枝Argonaute蛋白与PIWI相互作用RNA（piRNA）相关，并沉默动物性腺中的转座因子。在这里，我们报告的晶体结构的蚕PIWI-进化枝Argonaute，Siwi，结合到内源性皮尔纳，在2.4埃的分辨率。Siwi采用由N-PAZ和MID-PIWI叶组成的双叶结构，其中结合的皮尔纳的50和30末端分别由MID-PIWI和PAZ结构域锚定。Siwi与AGO进化枝Argonautes的结构比较揭示了它们的核酸结合通道的显著差异，这可能反映了它们的指导RNA的不同长度以及它们在指导RNA加载和切割产物释放方面的机制差异。此外，结构揭示了Siwi和原核生物，但不是真核生物，AGO进化枝Argonautes具有意想不到的相似性，例如金属依赖的5 '-磷酸识别和催化四分体形成期间的潜在结构转变。总的来说，这项研究为理解piRNA介导的转座子沉默的机制提供了一个关键的起点。
PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 angstrom resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 50 and 30 ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5'-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing.