Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.
Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.
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SLIP1-SLBP 的结构和生化研究确定 DBP5 和 eIF3g 为 SLIP1 结合蛋白。
DOI：
10.1093/nar/gkt558
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发表时间：
2013
影响因子：
14.9
通讯作者：
Conti,Elena
中科院分区：
文献类型：
--
作者：
vonMoeller,Holger;Lerner,Rachel;Ricciardi,Adele;Basquin,Claire;Marzluff,WilliamF;Conti,Elena
在后生动物中，依赖复制的组蛋白mRNA以茎环结构结束，而不是所有其他成熟mRNA的poly（A）尾特征。这个特殊的3′端被茎环结合蛋白（SLBP）结合，SLBP是一种参与组蛋白mRNA核输出和翻译的蛋白质。SLBP的翻译活性是通过与SLIP 1相互作用来介导的，SLIP 1是与翻译起始有关的终末因子4G（MIF 4G）样蛋白的中间结构域。我们确定了与SLBP的抑制-激活结构域结合的斑马鱼SLIP 1的2.5 μ m分辨率晶体结构，并确定了识别的决定因素。我们在另外两种蛋白质中发现了SLIP 1结合基序（SBM）：翻译起始因子eIF 3g和mRNA输出因子DBP 5。我们通过下拉测定法证实了SLIP 1与DBP 5和eIF 3g的结合，并确定了与DBP 5 SBM结合的SLIP 1的3.25 nm分辨率结构。SLIP 1的SBM结合和同源二聚化残基在CBP 80/20依赖性翻译起始因子（CTIF）的MIF 4G结构域中是保守的。结果表明SLIP 1同源二聚体或SLIP 1-CTIF异源二聚体如何可以作为平台来桥接SLBP与参与mRNA代谢的不同步骤的含SBM的蛋白质。
In metazoans, replication-dependent histone mRNAs end in a stem-loop structure instead of the poly(A) tail characteristic of all other mature mRNAs. This specialized 3′ end is bound by stem-loop binding protein (SLBP), a protein that participates in the nuclear export and translation of histone mRNAs. The translational activity of SLBP is mediated by interaction with SLIP1, amiddle domain ofinitiationfactor4G(MIF4G)-like protein that connects to translation initiation. We determined the 2.5 Å resolution crystal structure of zebrafish SLIP1 bound to the translation–activation domain of SLBP and identified the determinants of the recognition. We discovered a SLIP1-binding motif (SBM) in two additional proteins: the translation initiation factor eIF3g and the mRNA-export factor DBP5. We confirmed the binding of SLIP1 to DBP5 and eIF3g by pull-down assays and determined the 3.25 Å resolution structure of SLIP1 bound to the DBP5 SBM. The SBM-binding and homodimerization residues of SLIP1 are conserved in the MIF4G domain of CBP80/20-dependent translation initiation factor (CTIF). The results suggest how the SLIP1 homodimer or a SLIP1–CTIF heterodimer can function as platforms to bridge SLBP with SBM-containing proteins involved in different steps of mRNA metabolism.