A novel peptide recognition mode revealed by the X-ray structure of a core U2AF-35/U2AF65 heterodimer
A novel peptide recognition mode revealed by the X-ray structure of a core U2AF-35/U2AF65 heterodimer
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DOI：
10.1016/s0092-8674(01)00480-9
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发表时间：
2001-09-07
期刊：
影响因子：
64.5
通讯作者：
Burley, SK
中科院分区：
文献类型：
--
作者：
Kielkopf, CL;Rodionova, NA;Burley, SK
U2辅助因子（U2AF）是识别3'剪接位点并招募U2 snRNP到分支点的必不可少的剪接因子。人类核心U2AF异源二聚体的x射线结构，由U2AF（35）中心结构域和U2AF（65）富含脯氨酸的区域组成，已在2.2埃分辨率下确定。该结构揭示了一种新的蛋白质蛋白质识别策略，其中U2AF（35）的非典型RNA识别基序（RRM）和U2AF（65）的脯氨酸片段通过相互的“舌槽”色氨酸残基相互作用。补充生化实验表明，核心U2AF异源二聚体与RNA结合，相互作用的色氨酸侧链对U2AF二聚化至关重要。其他剪接因子中的非典型rrm可能在剪接体组装过程中作为其他地方的蛋白质相互作用基序。
U2 auxiliary factor (U2AF) is an essential splicing factor that recognizes the 3' splice site and recruits the U2 snRNP to the branch point. The X-ray structure of the human core U2AF heterodimer, consisting of the U2AF(35) central domain and a proline-rich region of U2AF(65), has been determined at 2.2 Angstrom resolution. The structure reveals a novel protein-protein recognition strategy, in which an atypical RNA recognition motif (RRM) of U2AF(35) and the U2AF(65) polyproline segment interact via reciprocal "tongue-in-groove" tryptophan residues. Complementary biochemical experiments demonstrate that the core U2AF heterodimer binds RNA, and that the interacting tryptophan side chains are essential for U2AF dimerization. Atypical RRMs in other splicing factors may serve as protein-protein interaction motifs elsewhere during spliceosome assembly.