A switch from α‐helical to β‐strand conformation during co‐translational protein folding
| Autor: | Xabier Agirrezabala, Ekaterina Samatova, Meline Macher, Marija Liutkute, Manisankar Maiti, David Gil‐Carton, Jiri Novacek, Mikel Valle, Marina V Rodnina |
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| Přispěvatelé: | Max Planck Society, European Research Council, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministry of Education, Youth and Sports (Czech Republic), German Rectors' Conference |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical Protein Folding General Immunology and Microbiology General Neuroscience Circular Dichroism Escherichia coli Proteins Cryoelectron Microscopy cotranslational folding nascent chain ribosome Ribosome General Biochemistry Genetics and Molecular Biology Nascent chain Protein Biosynthesis Cotranslational folding Cold Shock Proteins and Peptides Escherichia coli Protein Conformation beta-Strand Molecular Biology Protein Processing Post-Translational Ribosomes |
| Zdroj: | The EMBO Journal |
| Popis: | 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. The work was funded by the Max Planck Society to M.V.R., the European Research Council (ERC) Advanced Investigator Grant RIBOFOLD to M.V.R. (proposal number n° 787926), and the Spanish Ministry of Economy and Competitiveness to X.A. (CTQ2015-73560-JIN) and to M.V. (PGC2018-098996-B-I00). We thank the Spanish Ministry of Science for the Severo Ochoa Excellence Accreditations to the CIC bioGUNE (SEV-2016-0644). CIISB research infrastructure project LM2018127 funded by MEYS CR is gratefully acknowledged for the financial support of the measurements at the CF Cryo-electron Microscopy and Tomography. Open Access funding enabled and organized by Projekt DEAL. |
| Databáze: | OpenAIRE |
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