The C-terminal alpha-alpha superhelix of Pat is required for mRNA decapping in metazoa.

The C-terminal alpha-alpha superhelix of Pat is required for mRNA decapping in metazoa.
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DOI:
10.1038/emboj.2010.124
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发表时间:
2010-07-21
期刊:
影响因子:
11.4
通讯作者:
Izaurralde, Elisa
Izaurralde, Elisa
中科院分区:
生物学1区
文献类型:
--
作者:
Braun, Joerg E.;Tritschler, Felix;Haas, Gabrielle;Igreja, Catia;Truffault, Vincent;Weichenrieder, Oliver;Izaurralde, Elisa

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Pat蛋白调节mRNA从抑制活性状态到被抑制状态的转变,使靶向mRNA降解。Pat蛋白含有保守的N-末端序列、富含脯氨酸的区域、Mid结构域和C-末端结构域(Pat-C)。我们发现,Pat-C是必不可少的相互作用与mRNA的decapping因子(即DCP 2,EDC 4和LSm 1 -7),而富P区和Mid域有不同的功能,在调节这些相互作用。DCP 2和EDC 4的结合通过富含P的区域增强,并且不需要LSm 1 -7。LSm 1 -7结合由Mid结构域辅助,并由富含P的区域减少。结构分析显示Pat-C折叠成α-α超螺旋,暴露了结构域一侧的保守和碱性残基。这种保守的碱性表面是RNA、DCP 2、EDC 4和LSm 1 -7结合所必需的。由Pat-C介导的相互作用的多样性表明,这些相互作用中的某些相互作用是相互排斥的,因此,Pat蛋白质切换脱帽伴侣,允许mRNA脱帽途径中的顺序步骤之间的转换。
Pat proteins regulate the transition of mRNAs from a state that is translationally active to one that is repressed, committing targeted mRNAs to degradation. Pat proteins contain a conserved N-terminal sequence, a proline-rich region, a Mid domain and a C-terminal domain (Pat-C). We show that Pat-C is essential for the interaction with mRNA decapping factors (i.e. DCP2, EDC4 and LSm1–7), whereas the P-rich region and Mid domain have distinct functions in modulating these interactions. DCP2 and EDC4 binding is enhanced by the P-rich region and does not require LSm1–7. LSm1–7 binding is assisted by the Mid domain and is reduced by the P-rich region. Structural analysis revealed that Pat-C folds into an α–α superhelix, exposing conserved and basic residues on one side of the domain. This conserved and basic surface is required for RNA, DCP2, EDC4 and LSm1–7 binding. The multiplicity of interactions mediated by Pat-C suggests that certain of these interactions are mutually exclusive and, therefore, that Pat proteins switch decapping partners allowing transitions between sequential steps in the mRNA decapping pathway.
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