Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis
Abstract Cotranslational protein folding depends on general chaperones that engage highly diverse nascent chains at the ribosomes. Here we discover a dedicated ribosome-associated chaperone, Chp1, that rewires the cotranslational folding machinery to assist in the challenging biogenesis of abundantl...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45645-w |
| _version_ | 1797273996236947456 |
|---|---|
| author | Melania Minoia Jany Quintana-Cordero Katharina Jetzinger Ilgin Eser Kotan Kathryn Jane Turnbull Michela Ciccarelli Anna E. Masser Dorina Liebers Eloïse Gouarin Marius Czech Vasili Hauryliuk Bernd Bukau Günter Kramer Claes Andréasson |
| author_facet | Melania Minoia Jany Quintana-Cordero Katharina Jetzinger Ilgin Eser Kotan Kathryn Jane Turnbull Michela Ciccarelli Anna E. Masser Dorina Liebers Eloïse Gouarin Marius Czech Vasili Hauryliuk Bernd Bukau Günter Kramer Claes Andréasson |
| author_sort | Melania Minoia |
| collection | DOAJ |
| description | Abstract Cotranslational protein folding depends on general chaperones that engage highly diverse nascent chains at the ribosomes. Here we discover a dedicated ribosome-associated chaperone, Chp1, that rewires the cotranslational folding machinery to assist in the challenging biogenesis of abundantly expressed eukaryotic translation elongation factor 1A (eEF1A). Our results indicate that during eEF1A synthesis, Chp1 is recruited to the ribosome with the help of the nascent polypeptide-associated complex (NAC), where it safeguards eEF1A biogenesis. Aberrant eEF1A production in the absence of Chp1 triggers instant proteolysis, widespread protein aggregation, activation of Hsf1 stress transcription and compromises cellular fitness. The expression of pathogenic eEF1A2 variants linked to epileptic-dyskinetic encephalopathy is protected by Chp1. Thus, eEF1A is a difficult-to-fold protein that necessitates a biogenesis pathway starting with dedicated folding factor Chp1 at the ribosome to protect the eukaryotic cell from proteostasis collapse. |
| first_indexed | 2024-03-07T14:52:05Z |
| format | Article |
| id | doaj.art-f23814c7fcb4463299135165d37e841c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:05Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f23814c7fcb4463299135165d37e841c2024-03-05T19:39:12ZengNature PortfolioNature Communications2041-17232024-02-0115111610.1038/s41467-024-45645-wChp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesisMelania Minoia0Jany Quintana-Cordero1Katharina Jetzinger2Ilgin Eser Kotan3Kathryn Jane Turnbull4Michela Ciccarelli5Anna E. Masser6Dorina Liebers7Eloïse Gouarin8Marius Czech9Vasili Hauryliuk10Bernd Bukau11Günter Kramer12Claes Andréasson13Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityCenter for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH AllianceDepartment of Clinical Microbiology, RigshospitaletDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityCenter for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH AllianceDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityScience for Life Laboratory, Department of Experimental Medical Science, Lund UniversityCenter for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH AllianceDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm UniversityAbstract Cotranslational protein folding depends on general chaperones that engage highly diverse nascent chains at the ribosomes. Here we discover a dedicated ribosome-associated chaperone, Chp1, that rewires the cotranslational folding machinery to assist in the challenging biogenesis of abundantly expressed eukaryotic translation elongation factor 1A (eEF1A). Our results indicate that during eEF1A synthesis, Chp1 is recruited to the ribosome with the help of the nascent polypeptide-associated complex (NAC), where it safeguards eEF1A biogenesis. Aberrant eEF1A production in the absence of Chp1 triggers instant proteolysis, widespread protein aggregation, activation of Hsf1 stress transcription and compromises cellular fitness. The expression of pathogenic eEF1A2 variants linked to epileptic-dyskinetic encephalopathy is protected by Chp1. Thus, eEF1A is a difficult-to-fold protein that necessitates a biogenesis pathway starting with dedicated folding factor Chp1 at the ribosome to protect the eukaryotic cell from proteostasis collapse.https://doi.org/10.1038/s41467-024-45645-w |
| spellingShingle | Melania Minoia Jany Quintana-Cordero Katharina Jetzinger Ilgin Eser Kotan Kathryn Jane Turnbull Michela Ciccarelli Anna E. Masser Dorina Liebers Eloïse Gouarin Marius Czech Vasili Hauryliuk Bernd Bukau Günter Kramer Claes Andréasson Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis Nature Communications |
| title | Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis |
| title_full | Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis |
| title_fullStr | Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis |
| title_full_unstemmed | Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis |
| title_short | Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis |
| title_sort | chp1 is a dedicated chaperone at the ribosome that safeguards eef1a biogenesis |
| url | https://doi.org/10.1038/s41467-024-45645-w |
| work_keys_str_mv | AT melaniaminoia chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT janyquintanacordero chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT katharinajetzinger chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT ilgineserkotan chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT kathrynjaneturnbull chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT michelaciccarelli chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT annaemasser chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT dorinaliebers chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT eloisegouarin chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT mariusczech chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT vasilihauryliuk chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT berndbukau chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT gunterkramer chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis AT claesandreasson chp1isadedicatedchaperoneattheribosomethatsafeguardseef1abiogenesis |