Crystal structure of yeast initiation factor 4A, a DEAD-box RNA helicase
Crystal structure of yeast initiation factor 4A, a DEAD-box RNA helicase
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DOI：
10.1073/pnas.97.24.13080
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发表时间：
2000-11-21
影响因子：
11.1
通讯作者：
McKay, DB
中科院分区：
文献类型：
--
作者：
Caruthers, JM;Johnson, ER;McKay, DB
真核细胞翻译起始因子4A(ElF4A)是DEA(D/H)盒RNA解旋酶家族的成员，是一组将ATPase活性与RNA结合和解离的蛋白质。以前的工作已经提供了elF4A的氨基末端的结构，即ATP结合域。扩展这些结果，我们已经解决了elF4A的羧基末端结构域的结构，数据达到1.75埃分辨率；它有一个平行的LY-P拓扑，它叠加在其他遥远相关的解旋酶的等价域的结构和保守基序上，只有很小的变化。利用2.8埃分辨率的数据和羧基末端结构域的精细模型进行分子置换，我们完成了全长elF4A的结构，它是由两个紧凑的结构域通过扩展的连接子连接而成的“哑铃”结构。通过使用其他解旋酶的结构作为模板，可以对elF4A的紧凑结构进行建模，该结构表明：(I)解旋酶基序IV与RNA结合；(Ii)Arg-298，它在DEA(D/H)-box RNA解旋酶家族中保守，但在许多其他解旋酶中缺失，也与RNA结合；(Iii)基序V和VI通过与ATP和DEA(D/H)基序的相互作用将羧基末端结构域与氨基末端结构域“连接”起来，提供了一种将ATP结合和水解酶与调节RNA结合的构象变化相结合的机制。
The eukaryotic translation initiation factor 4A (elF4A) is a member of the DEA(D/H)-box RNA helicase family, a diverse group of proteins that couples an ATPase activity to RNA binding and unwinding. Previous work has provided the structure of the amino-terminal, ATP-binding domain of elF4A. Extending those results, we have solved the structure of the carboxyl-terminal domain of elF4A with data to 1.75 Angstrom resolution; it has a parallel LY-P topology that superimposes, with minor variations, on the structures and conserved motifs of the equivalent domain in other, distantly related helicases. Using data to 2.8 Angstrom resolution and molecular replacement with the refined model of the carboxyl-terminal domain, we have completed the structure of full-length elF4A; it is a "dumbbell" structure consisting of two compact domains connected by an extended linker. By using the structures of other helicases as a template, compact structures can be modeled for elF4A that suggest (i) helicase motif IV binds RNA; (ii) Arg-298, which is conserved in the DEA(D/H)-box RNA helicase family but is absent from many other helicases, also binds RNA; and (iii) motifs V and VI "link" the carboxyl-terminal domain to the amino-terminal domain through interactions with ATP and the DEA(D/H) motif, providing a mechanism for coupling ATP binding and hydrolysis with conformational changes that modulate RNA binding.