A switch from α‐helical to β‐strand conformation during co‐translational protein folding
Open Access
- 7 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 41 (4), e109175
- https://doi.org/10.15252/embj.2021109175
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.Keywords
Funding Information
- H2020 European Research Council (787926)
This publication has 70 references indexed in Scilit:
- A biphasic pulling force acts on transmembrane helices during translocon-mediated membrane integrationNature Structural & Molecular Biology, 2012
- Kinetic Analysis of Ribosome-bound Fluorescent Proteins Reveals an Early, Stable, Cotranslational Folding IntermediateOnline Journal of Public Health Informatics, 2012
- Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopyProceedings of the National Academy of Sciences of the United States of America, 2010
- Structure of the 70S ribosome bound to release factor 2 and a substrate analog provides insights into catalysis of peptide releaseProceedings of the National Academy of Sciences of the United States of America, 2010
- Insights into substrate stabilization from snapshots of the peptidyl transferase center of the intact 70S ribosomeNature Structural & Molecular Biology, 2009
- Tertiary interactions within the ribosomal exit tunnelNature Structural & Molecular Biology, 2009
- Cotranslational Folding Promotes β-Helix Formation and Avoids Aggregation In VivoJournal of Molecular Biology, 2008
- Rare Codons ClusterPLOS ONE, 2008
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004