Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis

• DOI: 10.1038/s41467-024-45645-w
• Publication Date: 2024-02-15T05:04:48Z
• Authors: Melania Minoia; Jany Quintana-Cor...; Katharina Jetzinger; Ilgin Eser Kotan; Kathryn Jane Turn...; Michela Ciccarelli; Anna E. Masser; Dorina Liebers; Eloïse Gouarin; Marius Czech; Vasili Hauryliuk; Bernd Bukau; Günter Kramer; Claes Andréasson
• Keywords: Chaperone (clinical); ribosome biogenesis; Proteostasis; CLPB; EIF4E; Ribosomal protein

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, rewires cotranslational machinery to assist in challenging biogenesis of abundantly expressed eukaryotic translation elongation factor 1A (eEF1A). Our results indicate during eEF1A synthesis, Chp1 is recruited ribosome with help polypeptide-associated complex (NAC), where it safeguards biogenesis. Aberrant production absence triggers instant proteolysis, widespread aggregation, activation Hsf1 stress transcription and compromises cellular fitness. The expression pathogenic eEF1A2 variants linked epileptic-dyskinetic encephalopathy protected by Chp1. Thus, difficult-to-fold necessitates pathway starting protect cell from proteostasis collapse.