Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity
Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity
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DOI：
10.1016/s1097-2765(04)00180-7
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发表时间：
2004-04-09
期刊：
影响因子：
16
通讯作者：
Lima, CD
中科院分区：
文献类型：
--
作者：
Gu, MG;Fabrega, C;Lima, CD
从降解的信使RNA中完全去除残留的N-7鸟嘌呤帽是必要的，以防止可能干扰RNA加工、输出和翻译的中间体的积累。人清除剂脱帽酶DcpS催化mRNA降解后的残余帽水解，释放N-7甲基鸟苷单磷酸和5 '-二磷酸封端的帽或mRNA产物。与m（7）GpppG或m（7）GpppA结合的DcpS结构揭示了不对称的DcpS二聚体，其同时产生开放的非生产性DcpS帽复合物和封闭的生产性DcpS帽复合物，其通过30埃结构域运动交替。结构和生化分析表明，一个自动调节机制，从而防止过早脱帽mRNA通过阻断所需的构象变化，形成一个封闭的生产活性位点能够帽水解。
Complete removal of residual N-7 guanine cap from degraded messenger RNA is necessary to prevent accumulation of intermediates that might interfere with RNA processing, export, and translation. The human scavenger decapping enzyme, DcpS, catalyzes residual cap hydrolysis following mRNA degradation, releasing N-7 methyl guanosine monophosphate and 5'-diphosphate terminated cap or mRNA products. DcpS structures bound to m(7)GpppG or m(7)GpppA reveal an asymmetric DcpS dimer that simultaneously creates an open nonproductive DcpS-cap complex and a closed productive DcpS-cap complex that alternate via 30 Angstrom domain movements. Structural and biochemical analysis suggests an autoregulatory mechanism whereby premature decapping mRNA is prevented by blocking the conformational changes that are required to form a closed productive active site capable of cap hydrolysis.