Cotranslational Folding of Protein Domains on the Ribosome

Abstract

Protein domains start to fold co-translationally, while they are being synthesized on the ribosome. Co-translational folding is vectorial; it starts in the confined space of the polypeptide exit tunnel of the ribosome and is modulated by the speed of translation. Defects in protein folding cause many human diseases; thus, understanding the co-translational folding is of eminent importance. We investigated co-translational folding of protein domains of different architecture in real-time as the protein is being synthesized by the ribosome. We showed that folding of the nascent protein proceeds through a several dynamic conformations that forms within and outside the peptide tunnel of the ribosome before exiting from the ribosome. The rate of translation defines the pathway and timing of folding. These results show how different protein domains fold co-translationally.