Co-translational assembly counteracts promiscuous interactions - addendum. Co-translational assembly counteracts promiscuous interactions - addendum

During the co-translational assembly of protein complexes, a fully synthesized subunit engages with the nascent chain of a newly synthesized interaction partner. Such events are thought to contribute to productive assembly, but their exact physiological relevance remains underexplored. Here, we examined structural motifs contained in nucleoporins for their potential to facilitate co-translational assembly. We experimentally tested candidate structural motifs and identified several previously unknown co-translational interactions. We demonstrate by selective ribosome profiling that domain invasion motifs of beta-propellers, coiled-coils, and short linear motifs act as co-translational assembly domains. Such motifs are often contained in proteins that are members of multiple complexes (moonlighters) and engage with closely related paralogs. Surprisingly, moonlighters and paralogs assembled co-translationally in only one but not all of the relevant assembly pathways. Our results highlight the regulatory complexity of assembly pathways.

在蛋白质复合物的共翻译组装过程中，一条已完全合成的亚基会与新合成的互作伴侣的新生肽链相结合。这类事件被认为可促进有效组装，但其确切的生理学相关功能仍未得到充分探索。本研究针对核孔蛋白（nucleoporins）所包含的结构基序，探究其促进共翻译组装的潜力。我们通过实验对候选结构基序进行了验证，鉴定出数种此前未被发现的共翻译互作关系。借助选择性核糖体谱分析（selective ribosome profiling），我们证实β螺旋桨结构域（beta-propellers）、卷曲螺旋结构（coiled-coils）以及短线性基序的结构入侵基序可作为共翻译组装结构域。这类基序常存在于同时参与多种复合物的蛋白质（即兼职蛋白moonlighters）中，且可与亲缘关系较近的旁系同源蛋白（paralogs）发生互作。令人意外的是，兼职蛋白与旁系同源蛋白仅在部分而非全部相关组装通路中发生共翻译组装。本研究结果凸显了蛋白质复合物组装通路的调控复杂性。