Co-translational assembly of mammalian nuclear multisubunit complexes
Co-translational assembly of mammalian nuclear multisubunit complexes
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DOI：
10.1038/s41467-019-09749-y
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发表时间：
2019-04-15
影响因子：
16.6
通讯作者：
Tora, Laszlo
中科院分区：
文献类型：
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作者：
Kamenova, Ivanka;Mukherjee, Pooja;Tora, Laszlo
细胞消耗大量的能量来构建蛋白质，这些蛋白质通常以严格控制化学计量的多蛋白质组装体的形式组织起来。由于编码组装成多亚基复合物的亚基的基因分散在真核生物的基因组中，因此尚不清楚这些蛋白质复合物如何组装。在这里，我们表明，哺乳动物核转录复合物（TFIID，TREX-2和佐贺）由大量的亚基组成，但缺乏精确的建筑细节共同构建。我们证明，二聚化结构域和它们在相互作用的亚基的位置决定了共翻译组装途径（同时或顺序）。缺乏共翻译相互作用可导致伴侣蛋白的降解。因此，蛋白质合成和复合物组装在构建哺乳动物多亚基复合物中是联系在一起的，这表明共翻译组装是哺乳动物细胞中避免非特异性相互作用和蛋白质聚集的一般原则。这些发现还将通过定义多亚基复合物结构中的内源性共翻译构建块来推进结构生物学。
Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling in a multi-subunit complex are dispersed in the genome of eukaryotes, it is unclear how these protein complexes assemble. Here, we show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits, but lacking precise architectural details are built co-translationally. We demonstrate that dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). The lack of co-translational interaction can lead to degradation of the partner protein. Thus, protein synthesis and complex assembly are linked in building mammalian multisubunit complexes, suggesting that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will also advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.