Large-scale induced fit recognition of an m7GpppG cap analogue by the human nuclear cap-binding complex
Large-scale induced fit recognition of an m7GpppG cap analogue by the human nuclear cap-binding complex
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DOI：
10.1093/emboj/cdf538
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发表时间：
2002-10-15
期刊：
影响因子：
11.4
通讯作者：
Cusack, S
中科院分区：
文献类型：
--
作者：
Mazza, C;Segref, A;Cusack, S
异二聚体核帽结合复合物 (CBC) 与细胞核中 RNA 的 5' 帽结构结合，并在其不同的成熟步骤中发挥核心作用。我们以 2.1 埃分辨率描述了与 m(7)GpppG 帽类似物结合的人 CBC 的晶体结构。与未复合的 CBC 的结构比较表明，帽子结合诱导了小亚基 CBP20 的 N 端和 C 端延伸至中央 RNP 结构域的约 50 个残基周围的二核苷酸的协同折叠。 CBP20 的帽结合构象通过与配体和亚基内的复杂相互作用网络以及 CBP20 N 末端尾部与大亚基 CBP80 的新相互作用来稳定。尽管其结构与其他已知的帽结合蛋白（例如细胞质帽结合蛋白 eIF4E）非常不同，但通过将碱基夹在两个芳香残基（在本例中为两个保守的酪氨酸）之间，再次实现了甲基化鸟苷的特异性。讨论了翻译起始所需的加帽 mRNA 转移至 eIF4E 的影响。
The heterodimeric nuclear cap-binding complex (CBC) binds to the 5' cap structure of RNAs in the nucleus and plays a central role in their diverse maturation steps. We describe the crystal structure at 2.1 Angstrom resolution of human CBC bound to an m(7)GpppG cap analogue. Comparison with the structure of uncomplexed CBC shows that cap binding induces co-operative folding around the dinucleotide of some 50 residues from the N- and C-terminal extensions to the central RNP domain of the small subunit CBP20. The cap-bound conformation of CBP20 is stabilized by an intricate network of interactions both to the ligand and within the subunit, as well as new interactions of the CBP20 N-terminal tail with the large subunit CBP80. Although the structure is very different from that of other known cap-binding proteins, such as the cytoplasmic cap-binding protein eIF4E, specificity for the methylated guanosine again is achieved by sandwiching the base between two aromatic residues, in this case two conserved tyrosines. Implications for the transfer of capped mRNAs to eIF4E, required for translation initiation, are discussed.