The twisted tale of cotranslational protein complex assembly.

Macromolecular complexes are cells' functional units, and their correct and efficient assembly is critical to life's processes. Complex assembly was classically described as the encounter of fully synthesized, mature protein subunits, yet an amalgam of current studies shows that cotranslational assembly is prevalent, in which nascent proteins vectorially form interfaces with their partners during translation. In this review, we examine the advances in this emerging field. We discuss the thermodynamic and kinetic principles underlying different modes of assembly and highlight how the specific structural/biophysical features of the corresponding complexes enable them. We propose that cotranslational assembly produces kinetically stable oligomeric states that resist dissociation and stochastic conformational changes, thereby conferring functionality amid molecular crowding or environmental stresses.