Crystal structure of the ATPase domain of translation initiation factor 4A from Saccharomyces cerevisiae -: the prototype of the DEAD box protein family
Crystal structure of the ATPase domain of translation initiation factor 4A from Saccharomyces cerevisiae -: the prototype of the DEAD box protein family
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DOI：
10.1016/s0969-2126(99)80088-4
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发表时间：
1999-06-15
期刊：
影响因子：
5.7
通讯作者：
Baumann, U
中科院分区：
文献类型：
--
作者：
Benz, J;Trachsel, H;Baumann, U
背景：翻译起始因子4A（translation initiation factor 4A，eIF 4A）是DEAD-box蛋白家族的原型。DEAD盒蛋白参与多种细胞过程，包括剪接、核糖体生物合成和RNA降解。来自ATP水解的能量用于在mRNA翻译起始期间进行RNA解旋。elF 4A的存在是需要的43 S preinitiation复合物结合和扫描的mRNA.Results：我们在这里提出的晶体结构的核苷酸结合域的elF 4A在2.0埃和结构与绑定腺苷二磷酸和腺苷三磷酸在2.2埃和2.4埃分辨率，分别。该酶的载脂蛋白形式的结构已由多个同晶置换确定。ATP酶结构域包含一个中央七链β折叠，两侧是九个α螺旋。尽管低的序列同源性的NTR结构域的RNA和DNA解旋酶，eIF 4A的三维折叠几乎是相同的DNA解旋酶PcrA嗜热脂肪芽孢杆菌和RNA解旋酶NS 3丙型肝炎病毒。结论：我们已经确定了晶体结构的N-末端结构域的eIF 4A从酵母作为第一个结构的DEAD盒蛋白家族的成员。蛋白质与结合的ADP和ATP的复合物提供了对ATP水解和能量转移到解链RNA的机制的深入了解。B的DNA解旋酶PcrA的ATP酶结构域的相同折叠。嗜热脂肪酸杆菌和丙型肝炎病毒的RNA解旋酶表明DExx-和DEAD-盒蛋白的所有ATP酶结构域的共同折叠。
Background: Translation initiation factor 4A (elF4A) is the prototype of the DEAD-box family of proteins. DEAD-box proteins are involved in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. Energy from ATP hydrolysis is used to perform RNA unwinding during initiation of mRNA translation. The presence of elF4A is required for the 43S preinitiation complex to bind to and scan the mRNA.Results: We present here the crystal structure of the nucleotide-binding domain of elF4A at 2.0 Angstrom and the structures with bound adenosinediphosphate and adenosinetriphosphate at 2.2 Angstrom and 2.4 Angstrom resolution, respectively. The structure of the apo form of the enzyme has been determined by multiple isomorphous replacement. The ATPase domain contains a central seven-stranded beta sheet flanked by nine a helices. Despite low sequence homology to the NTPase domains of RNA and DNA helicases, the three-dimensional fold of elF4A is nearly identical to the DNA helicase PcrA of Bacillus stearothermophilus and to the RNA helicase NS3 of hepatitis C virus.Conclusions: We have determined the crystal structure of the N-terminal domain of the elF4A from yeast as the first structure of a member of the DEAD-box protein family. The complex of the protein with bound ADP and ATP offers insight into the mechanism of ATP hydrolysis and the transfer of energy to unwind RNA. The identical fold of the ATPase domain of the DNA helicase PcrA of B. stearothermophilus and the RNA helicase of hepatitis C virus suggests a common fold for all ATPase domains of DExx- and DEAD-box proteins.