The majority of cellular proteins do not function alone, but act together as complexes to achieve concerted functions. Despite the prevalence of protein complexes, very little is known about the mechanisms that ensure their correct folding and assembly in the crowded eukaryotic cell. The importance of this folding challenge is underscored by the growing number of diseases caused by misfolded proteins, which are often characterized by aggregation of ‘lonely’, unassembled complex subunits.

In the early 1960s, pioneering work by David Zipser and by Yukio Kiho and Alexander Rich suggested that protein-complex assembly is coordinated with protein synthesis. Each lab studied the assembly process of a ‘model’ complex, the β-galactosidase homo-tetramer. Using bacterial lysates, they independently identified that the activity of the enzyme can already be detected during its synthesis. By following the kinetics of β-galactosidase activity during translation, they found that the nascent enzyme can oligomerize and that its activity is induced before synthesis is complete.