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首页> 外文期刊>Journal of Molecular Biology >Crystal structure of the Cmr2-Cmr3 subcomplex in the CRISPR-Cas RNA silencing effector complex
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Crystal structure of the Cmr2-Cmr3 subcomplex in the CRISPR-Cas RNA silencing effector complex

机译:CRISPR-Cas RNA沉默效应复合物中Cmr2-Cmr3亚复合物的晶体结构

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摘要

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci found in prokaryotes are transcribed to produce CRISPR RNAs (crRNAs) that, together with CRISPR-associated (Cas) proteins, target and degrade invading genetic materials. Cmr proteins (Cmr1-6) and crRNA form a sequence-specific RNA silencing effector complex. Here, we report the crystal structures of the Pyrococcus furiosus Cmr2-Cmr3 subcomplex bound with nucleotides (3′-AMP or ATP). The association of Cmr2 and Cmr3 forms an idiosyncratic crevasse, which binds the nucleotides. Cmr3 shares structural similarity with Cas6, which cleaves precursor crRNA for maturation, suggesting the divergent evolution of these proteins. Due to the structural resemblance, the properties of the RNA binding surface observed in Cas6 are well conserved in Cmr3, indicating the RNA binding ability of Cmr3. This surface of Cmr3 constitutes the crevasse observed in the Cmr2-Cmr3 complex. Our findings suggest that the Cmr2-Cmr3 complex uses the crevasse to bind crRNA and/or substrate RNA during the reaction.
机译:原核生物中发现的簇状,规则间隔,短回文重复(CRISPR)基因座被转录产生CRISPR RNA(crRNA),与CRISPR相关(Cas)蛋白一起靶向并降解入侵的遗传物质。 Cmr蛋白(Cmr1-6)和crRNA形成序列特异性RNA沉默效应子复合物。在这里,我们报告与核苷酸(3'-AMP或ATP)结合的激烈热球菌Cmr2-Cmr3亚复合物的晶体结构。 Cmr2和Cmr3的缔合形成特异的缝隙,该缝隙结合核苷酸。 Cmr3与Cas6共享结构相似性,Cas6裂解前体crRNA使其成熟,表明这些蛋白质的发散进化。由于结构相似,在Cas6中观察到的RNA结合表面的特性在Cmr3中非常保守,表明Cmr3的RNA结合能力。 Cmr3的表面构成在Cmr2-Cmr3复合物中观察到的裂缝。我们的发现表明,Cmr2-Cmr3复合物在反应过程中使用缝隙结合crRNA和/或底物RNA。

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