Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly
Protein complex assembly in the crowded cellular environment is a problem of greatest importance. A new study published in Science now reveals the existence and prevalence of a co-translational protein assembly mechanism in human cells: co-co assembly. Pairs of ribosomes ("disomes") translating the same mRNA become connected by nascent polypeptide chains, which assemble during the translation process as soon as their dimerisation interface emerges from the ribosome. Co-co assembly increases the fidelity of homo-oligomers formation by avoiding free diffusion of newly synthesized proteins and preventing assembly with unwanted partners.
One of the protein domains that facilitates co-co assembly is the coiled-coil, which I imagine as a zipper, fastening from the N-terminus while the rest is still emerging from the ribosome and folding. This process is not unique to coiled-coils, as other dimerisation domains can assemble co-translationally. Importantly, co-co assembly facilitates homodimerisation as, for instance, the nascent red zipper will only fasten to an identical zipper encoded by the same mRNA and not to the blue one at the back. All of this happens in a very busy cell, where lots of proteins are translated, fold and diffuse at any given time!
Bertolini M, Fenzl K, Kats I, Wruck F, Tippmann F, Schmitt J, Auburger JJ, Tans S, Bukau B, Kramer G. Interactions between nascent proteins translated by adjacent ribosomes drive homomer assembly. Science. 2021 Jan 1;371(6524):57-64. doi: 10.1126/science.abc7151. PMID: 33384371.