Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization
Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization
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DOI：
10.1016/s1097-2765(02)00555-5
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发表时间：
2002-06-01
期刊：
影响因子：
16
通讯作者：
Burley, SK
中科院分区：
文献类型：
--
作者：
Groft, CM;Burley, SK
轮状病毒（Rotaviruses）是一种节段双链RNA病毒，在非结构蛋白3（nonstructural protein 3，NSP 3）的帮助下，参与真核生物的翻译机制，非结构蛋白3是轮状病毒的细胞多聚腺苷酸结合蛋白（polyA binding protein，PABP）的功能同源物。NSP 3与病毒mRNA 3'共有序列结合，并通过与eIF 4G的相互作用使mRNA环化。在这里，我们提出了识别eIF 4GI片段的NSP 3的C-末端结构域（NSP 3-C）的X射线结构。NSP 3-C的同源二聚化产生对称的、细长的、主要是α-螺旋的结构，在二聚体界面处具有两个疏水性eIF 4G结合口袋。定点诱变和等温滴定量热法证明，NSP 3和PABP使用类似的eIF 4G识别策略，尽管在三级结构上存在显著差异。
Rotaviruses, segmented double-stranded RNA viruses, co-opt the eukaryotic translation machinery with the aid of nonstructural protein 3 (NSP3), a rotaviral functional homolog of the cellular poly(A) binding protein (PABP). NSP3 binds to viral mRNA 3' consensus sequences and circularizes mRNA via interactions with eIF4G. Here, we present the X-ray structure of the C-terminal domain of NSP3 (NSP3-C) recognizing a fragment of eIF4GI. Homodimerization of NSP3-C yields a symmetric, elongated, largely alpha-helical structure with two hydrophobic eIF4G binding pockets at the dimer interface. Site-directed mutagenesis and isothermal titration calorimetry documented that NSP3 and PABP use analogous eIF4G recognition strategies, despite marked differences in tertiary structure.