Department of Molecular Sociology, Max Planck Institute of Biophysics, Frankfurt, Germany.
Faculty of Bioscience, Heidelberg University, Heidelberg, Germany.
Nat Commun. 2022 Mar 9;13(1):1224. doi: 10.1038/s41467-022-28878-5.
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 examine structural motifs contained in nucleoporins for their potential to facilitate co-translational assembly. We experimentally test candidate structural motifs and identify 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 may 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 assemble co-translationally in only some but not all of the relevant biogenesis 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，一个完全合成的亚基与新合成的相互作用伙伴的新生链结合。这些事件被认为有助于有效的组装，但它们的确切生理相关性仍未得到充分探索。在这里，我们研究核孔蛋白中包含的结构基序，以探索它们促进共翻译组装的潜力。我们通过实验测试候选结构基序，并确定了几个以前未知的共翻译相互作用。我们通过选择性核糖体分析证明，β-旋转桨、卷曲螺旋和短线性基序的结构域入侵基序可能作为共翻译组装结构域。这些基序通常存在于多个复合物的成员（兼职者）中，并与密切相关的同源物相互作用。令人惊讶的是，兼职者和同源物仅在一些而不是所有相关生物发生途径中进行共翻译组装。我们的结果强调了组装途径的调节复杂性。
