Co-translational assembly orchestrates competing biogenesis pathways

• DOI: 10.1038/s41467-022-28878-5
• Publication Date: 2022-03-09T11:03:12Z
• Authors: Maximilian Seidel; Anja Becker; Filipa Pereira; Jonathan J. M. La...; Nayara Trevisan D...; Claudia M. Fusco; Eva Kaindl; Natalie Romanov; Janina Baumbach; Julian D. Langer; Erin M. Schuman; Kiran Raosaheb Patil; Gerhard Hummer; Vladimir Benes; Martin Beck
• Keywords: 570; 0303 health sciences; Science; /82/58; ddc:530; Q; /631/45/500; article; /38/90; Proteins; 530; Article; /38/91; 03 medical and health sciences; Protein Domains; Protein Biosynthesis; 616; /38/88; /631/80/389/2029; /631/337/574; ddc:570; /631/1647/514/1949; Ribosomes

AbstractDuring 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.