Structural analysis of the quaking homodimerization interface.
Structural analysis of the quaking homodimerization interface.
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DOI：
10.1016/j.jmb.2012.08.027
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发表时间：
2012-11-09
影响因子：
5.6
通讯作者：
Williamson, James R.
中科院分区：
文献类型：
--
作者：
Beuck, Christine;Qu, Song;Fagg, W. Samuel;Ares, Manuel, Jr.;Williamson, James R.
Quaking蛋白是星星蛋白家族的典型成员，通过调控mRNA的翻译、稳定性和剪接等在转录后基因调控中发挥重要作用。QkI-5已被证明可调节中枢神经系统中的mRNA表达，但对其在其他组织中的作用知之甚少。星星蛋白作为二聚体发挥功能，并与二分RNA序列结合，然而，同源和异源二聚体的结构和功能作用仍不清楚。在这里，我们提出了QkI二聚化结构域的晶体结构，它采用了类似的堆叠螺旋-转角-螺旋排列作为其同系物GLD-1和Sam 68，但不同的是插入在二聚体界面的额外的螺旋。二聚体界面残基的可变性可能通过防止与细胞中的非同源星星家族蛋白缔合来确保选择性同源二聚化。抑制二聚化的突变还显著损害体外RNA结合，改变QkI-5蛋白水平，并损害体内剪接测定中的QkI功能。总之，我们的研究结果表明，一个功能性的α 1同源二聚化结构域是需要在哺乳动物细胞中的QkI-5功能。
Quaking is a prototypical member of the STAR protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences, however, the structural and functional roles of homo- and hetero-dimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 and Sam68, but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels, and impair QkI function in a splicing assay in vivo. Together our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
DOI：
10.1107/s0907444904019158
发表时间：
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