Large protein complex interfaces have evolved to promote cotranslational assembly.
Large protein complex interfaces have evolved to promote cotranslational assembly.
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DOI：
10.7554/elife.79602
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发表时间：
2022-07-28
期刊：
影响因子：
7.7
通讯作者：
Rodnina, Marina, V
中科院分区：
文献类型：
--
作者：
Badonyi, Mihaly;Marsh, Joseph A.;Rodnina, Marina, V
关键词：
蛋白质复合物的组装途径应该是精确和有效的，以最大限度地减少错误折叠和与细胞中其他蛋白质的不必要的相互作用。实现这种效率的一种方法是在翻译期间通过亚基的共翻译组装来播种组装途径。虽然最近的证据表明，这种共翻译组装是普遍的，很少有人知道与现象相关的蛋白质复合物的属性。在这里，使用蛋白质组特异性蛋白质复合物结构和公开可用的核糖体分析数据的组合，我们表明，共翻译组装是特别常见的亚基之间形成大的分子间界面。为了测试大接口是否已经进化到促进共翻译组装，而不是共翻译组装是大接口的非适应性后果，我们比较了细菌，酵母和人类复合物中异聚亚基的第一个和最后一个翻译接口的大小。当考虑到所有在一起，我们观察到的N-末端接口大于C-末端接口的54%的时间，增加到64%，当我们排除只有小的接口，这是不太可能聚集组装的亚基。这有力地表明，大接口已演变为一种手段，以最大限度地提高成功的共翻译亚基结合的机会。
Assembly pathways of protein complexes should be precise and efficient to minimise misfolding and unwanted interactions with other proteins in the cell. One way to achieve this efficiency is by seeding assembly pathways during translation via the cotranslational assembly of subunits. While recent evidence suggests that such cotranslational assembly is widespread, little is known about the properties of protein complexes associated with the phenomenon. Here, using a combination of proteome-specific protein complex structures and publicly available ribosome profiling data, we show that cotranslational assembly is particularly common between subunits that form large intermolecular interfaces. To test whether large interfaces have evolved to promote cotranslational assembly, as opposed to cotranslational assembly being a non-adaptive consequence of large interfaces, we compared the sizes of first and last translated interfaces of heteromeric subunits in bacterial, yeast, and human complexes. When considering all together, we observe the N-terminal interface to be larger than the C-terminal interface 54% of the time, increasing to 64% when we exclude subunits with only small interfaces, which are unlikely to cotranslationally assemble. This strongly suggests that large interfaces have evolved as a means to maximise the chance of successful cotranslational subunit binding.