A divergent Sm fold in EDC3 proteins mediates DCPI binding and P-body targeting
A divergent Sm fold in EDC3 proteins mediates DCPI binding and P-body targeting
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DOI：
10.1128/mcb.01506-07
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发表时间：
2007-12-01
影响因子：
5.3
通讯作者：
Weichenrieder, Oliver
中科院分区：
文献类型：
--
作者：
Tritschler, Felix;Eulalio, Ana;Weichenrieder, Oliver
(L)Sm（Sm 和 Sm 样）蛋白家族的成员存在于所有生命领域，并在 RNA 代谢中发挥着至关重要的作用。 P-body 成分 EDC3（脱帽 3 的增强子）是该家族的一个不同成员，在 mRNA 脱帽中发挥作用。 EDC3由N端LSm结构域、中央FDF结构域和C端YjeF-N结构域组成。我们证明，这种模块化架构使 EDC3 能够与开盖机械的多个组件交互，包括 DCP1、DCP2 和 Me31B。 LSm 结构域介导 DCP1 结合和 P 体定位。我们确定了果蝇和人类 EDC3 LSm 结构域的三维结构，并表明该结构域采用不同的 Sm 折叠，缺乏特征性的 N 端 α 螺旋，并具有中断的 β 4 链。该结构域在溶液中保持单体状态，并且缺乏规范 (L)Sm 结构域结合 RNA 所需的几个特征。这些结构还揭示了一个保守的表面残基片段，这些残基是与 DCPI 相互作用所必需的，但不是 P 体定位所必需的。表面和关键结构残基的保守性表明 EDC3 蛋白中的 LSm 结构域采用相似的折叠，具有典型 (L)Sm 蛋白中不存在的可分离的新功能。
Members of the (L)Sm (Sm and Sm-like) protein family are found across all kingdoms of life and play crucial roles in RNA metabolism. The P-body component EDC3 (enhancer of decapping 3) is a divergent member of this family that functions in mRNA decapping. EDC3 is composed of a N-terminal LSm domain, a central FDF domain, and a C-terminal YjeF-N domain. We show that this modular architecture enables EDC3 to interact with multiple components of the decapping machinery, including DCP1, DCP2, and Me31B. The LSm domain mediates DCP1 binding and P-body localization. We determined the three-dimensional structures of the LSm domains of Drosophila melanogaster and human EDC3 and show that the domain adopts a divergent Sm fold that lacks the characteristic N-terminal alpha-helix and has a disrupted beta 4-strand. This domain remains monomeric in solution and lacks several features that canonical (L)Sm domains require for binding RNA. The structures also revealed a conserved patch of surface residues that are required for the interaction with DCPI but not for P-body localization. The conservation of surface and of critical structural residues indicates that LSm domains in EDC3 proteins adopt a similar fold that has separable novel functions that are absent in canonical (L)Sm proteins.