Interface size drives cotranslational assembly of protein complexes

Abstract

Summary Assembly pathways of protein complexes should be precise and efficient to minimise misfolding and unwanted interactions with other proteins in the cell. One way to achieve this is by seeding complex assembly during translation via nascent chain engagement. Here, we considered the possibility that the propensity of subunits to cotranslationally assemble is ingrained within the interface hierarchy of protein complexes. Using a combination of proteome-specific structure data and assembly-onset positions determined by ribosome profiling, we show that larger interfaces are prioritised in the course of cotranslational assembly. We observe that this effect is not exclusive to homomeric complexes, but appears to drive the assembly of heteromeric subunits, to the extent that interface size differences are detectable between N and C-terminal locations, with the former being larger on average. We provide explanations to this phenomenon and discuss its importance in a biological context.