Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France.
Centre National de la Recherche Scientifique (UMR7104), 67404, Illkirch, France.
Nat Commun. 2019 Apr 15;10(1):1740. doi: 10.1038/s41467-019-09749-y.
Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling in a multisubunit 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.
细胞投入大量的能量来构建蛋白质，这些蛋白质通常以具有严格调控的化学计量比的多蛋白复合物的形式存在。由于真核生物中编码亚基组装成多亚基复合物的基因分散在基因组中，因此这些蛋白复合物是如何组装的还不清楚。在这里，我们表明，由大量亚基组成的哺乳动物核转录复合物（TFIID、TREX-2 和 SAGA），尽管缺乏精确的结构细节，但却是共翻译组装的。我们证明，相互作用亚基中的二聚化结构域及其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会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，推进结构生物学的发展。
