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Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains.

ABSTRACT: Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples. We generated RPL39L knock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread autophagy. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.

SUBMITTER: Banerjee A

PROVIDER: S-EPMC11347166 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains.

Banerjee Arka A Ataman Meric M Smialek Maciej Jerzy MJ Mookherjee Debdatto D Rabl Julius J Mironov Aleksei A Mues Lea L Enkler Ludovic L Coto-Llerena Mairene M Schmidt Alexander A Boehringer Daniel D Piscuoglio Salvatore S Spang Anne A Mittal Nitish N Zavolan Mihaela M

Nucleic acids research 20240801 15

Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples. We generated RPL39L k ...[more]

PMID: 39041433

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Project description:Protein conformations in cells are not solely determined by amino acid sequences; they also depend on cellular environments. For instance, the ribosome tunnel induces its specific α-helix formation during cotranslational folding. Owing to the link between these temporally α-helix and biological functions, the mechanism of α-helix formation inside the ribosome tunnel has been previously explored. Consequently, the conformational restrictions of the tunnel were considered one of the driving forces of α-helix formation. Conversely, the ribosomal tunnel environment, including its chemical properties, appears to influence the α-helix formation. However, a comprehensive analysis of the ribosome tunnel environment's impact on the α-helix formation has not been conducted yet due to challenges in experimentally controlling it. Therefore, as a new computational approach, we proposed a ribosome environment-mimicking model (REMM) based on the radius and components of the experimentally determined ribosome tunnel structures. Using REMM, we assessed the impact of the ribosome tunnel environment on α-helix formation. Herein, we employed carbon nanotubes (CNT) as a reference model alongside REMM because CNT reproduce conformational restrictions rather than the ribosome tunnel environment. Quantitatively, the ability to reproduce the α-helix of nascent peptides in the experimental structure was compared between the CNT and REMM using enhanced all-atom molecular dynamics simulations. Consequently, the REMM more accurately reproduced the α-helix of the nascent peptides than the CNT, highlighting the significance of the ribosome tunnel environment in α-helix formation. Additionally, we analyzed the properties of the peptide inside each model to reveal the mechanism of ribosome tunnel-specific α-helix formation. Consequently, we revealed that the chemical diversities of the tunnel are essential for the formation of backbone-to-backbone hydrogen bonds in the peptides. In conclusion, the ribosome tunnel environment, with the diverse chemical properties, drives its specific α-helix formation. By proposing REMM, we newly provide the technical basis for investigating the protein conformations in various cellular environments.

Dataset Information

Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains.

Publications

Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains.

Similar Datasets

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