A switch from α‐helical to β‐strand conformation during co‐translational protein folding. (7th January 2022)

• Record Type: Journal Article
• Authors: Agirrezabala, Xabier; Samatova, Ekaterina; Macher, Meline; Liutkute, Marija; Maiti, Manisankar; Gil‐Carton, David; Novacek, Jiri; Valle, Mikel; Rodnina, Marina V
• Is Part Of: EMBO journal. Volume 41:Number 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-07
• Subjects: cotranslational folding -- nascent chain -- ribosome; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021109175
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo‐EM structure determination to show that folding of a β‐barrel protein begins with formation of a dynamic α‐helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N‐terminal part of the nascent chain refolds to a β‐hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α‐helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl‐transferase center suggest that protein folding could modulate ribosome activity. SYNOPSIS: Folding of nascent peptide chains is defined not only by their amino acid sequence but also by their interaction with the ribosome. Here, cotranslational folding of a small β‐structured protein is found to involve formation of a highly dynamic α‐helix inside the ribosome exit tunnel. Cotranslational folding of a small β‐structured protein is described in real time using a combination of biophysical, biochemical, and structural methods. Inside the exit tunnel, the β‐structured protein forms a highly dynamic α‐helix. The helical module transitions toward the β conformation as the nascent chain reaches the exit port. Different conformations of the nascent chain correlate with reorientation of key residues at the peptidyl‐transferase center of the ribosome. Abstract : Co‐translational folding of a small β‐structured protein involves formation of a highly dynamic α‐helix inside the ribosome exit tunnel.