Cotranslational processing mechanisms: towards a dynamic 3D model

Recent major advances have been made in understanding how cotranslational events are achieved in the course of protein biosynthesis. Specifically, several studies have shed light into the dynamic process of how nascent chains emerging from the ribosome are supported by protein biogenesis factors to ensure both processing and folding mechanisms. To take into account the awareness that coordination is needed, a new ‘concerted model’ recently proposed simultaneous action of both processes on the ribosome. In the model, any emerging nascent chain is first encountered by the chaperone trigger factor (TF), which forms an open cradle underneath the ribosomal exit tunnel. This cradle serves as a passive router that channels the nascent chains to the first cotranslational event, the proteolysis event performed by the N-terminal methionine excision machinery. Although fascinating, this model clearly raises more questions than it answers. Does the data used to develop this model stand up to scrutiny and, if not, what are the alternative mechanisms that the data suggest?