Most newly synthesized proteins associate into macromolecular complexes to become functional. Complex formation requires that subunits find each other in the crowded cellular environment while avoiding unspecific interactions and aggregation. Recent findings indicate that native complex formation is facilitated by coupling protein synthesis by ribosomes (translation) with folding and assembly. Studies analyzing formation of heteromeric complexes have elucidated the cotranslational engagement of nascent subunits by their fully translated, diffusing partner proteins (co-post assembly). We considered an alternative assembly mechanism that involves the interaction of two nascent subunits during their concurrent translation (co-co assembly) and thereby uncouples assembly from subunit diffusion. Provided that the interacting subunits are synthetized on one polysome, co-co assembly would increase the fidelity of homomer formation, prevent non-specific interactions with structural homologs and isoforms, and facilitate spatial and temporal coordination of the process. Whether cells employ co-co assembly as a general strategy for complex assembly, when and how efficiently nascent subunits interact, and what mechanisms are driving the process remain unclear.

European Union Horizon 2020 , NWO

Bertolini, M, Fenzl, K, Kats, I, Wruck, F, Tippmann, F, Schmitt, J, … Kramer, G. (2021). Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly. Science, 371(6524), 57–64. doi:10.1126/science.abc7151