TY  - JOUR
AU  - Minoia, Melania
AU  - Quintana-Cordero, Jany
AU  - Jetzinger, Katharina
AU  - Kotan, Ilgin Eser
AU  - Turnbull, Kathryn Jane
AU  - Ciccarelli, Michela
AU  - Masser, Anna E
AU  - Liebers, Dorina
AU  - Gouarin, Eloïse
AU  - Czech, Marius
AU  - Hauryliuk, Vasili
AU  - Bukau, Bernd
AU  - Kramer, Günter
AU  - Andréasson, Claes
TI  - Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-00398
SP  - 1382
PY  - 2024
N1  - DKFZ-ZMBH Alliance
AB  - 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.
KW  - Ribosomes: genetics
KW  - Ribosomes: metabolism
KW  - Protein Folding
KW  - Proteostasis
KW  - Eukaryotic Cells: metabolism
KW  - Protein Biosynthesis
LB  - PUB:(DE-HGF)16
C6  - pmid:38360885
C2  - pmc:PMC10869706
DO  - DOI:10.1038/s41467-024-45645-w
UR  - https://inrepo02.dkfz.de/record/288534
ER  -