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Article Dans Une Revue PLoS Genetics Année : 2023

Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import

Salomé Nashed
  • Fonction : Auteur
Houssam El Barbry
  • Fonction : Auteur
Médine Benchouaia
  • Fonction : Auteur
Angélie Dijoux-Maréchal
  • Fonction : Auteur
Thierry Delaveau
Nadia Ruiz-Gutierrez
Lucie Gaulier
  • Fonction : Auteur
Déborah Tribouillard-Tanvier
  • Fonction : Auteur
Guillaume Chevreux
  • Fonction : Auteur
Stéphane Le Crom
Frédéric Devaux
  • Fonction : Auteur
Elodie Laine
Mathilde Garcia

Résumé

N-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed an in-silico approach to detect functional preferences in cellular N-terminomes, and identified in S . cerevisiae more than 200 Gene Ontology terms with specific N-terminal signatures. In particular, we discovered that Mitochondrial Targeting Sequences (MTS) show a strong and specific over-representation at position 2 of hydrophobic residues known to define potential substrates of the N-terminal acetyltransferase NatC. We validated mitochondrial precursors as co-translational targets of NatC by selective purification of translating ribosomes, and found that their N-terminal signature is conserved in Saccharomycotina yeasts. Finally, systematic mutagenesis of the position 2 in a prototypal yeast mitochondrial protein confirmed its critical role in mitochondrial protein import. Our work highlights the hydrophobicity of MTS N-terminal residues and their targeting by NatC as important features for the definition of the mitochondrial proteome, providing a molecular explanation for mitochondrial defects observed in yeast or human NatC-depleted cells. Functional mapping of N-terminal residues thus has the potential to support the discovery of novel mechanisms of protein regulation or targeting.
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hal-04236040 , version 1 (10-10-2023)

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Salomé Nashed, Houssam El Barbry, Médine Benchouaia, Angélie Dijoux-Maréchal, Thierry Delaveau, et al.. Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import. PLoS Genetics, 2023, 19 (8), pp.e1010848. ⟨10.1371/journal.pgen.1010848⟩. ⟨hal-04236040⟩
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