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Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import.
- Source :
- PLoS Genetics, Vol 19, Iss 8, p e1010848 (2023)
- Publication Year :
- 2023
- Publisher :
- Public Library of Science (PLoS), 2023.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 15537390 and 15537404
- Volume :
- 19
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Genetics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.27f57877027b4bf1a96a603d340084e3
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pgen.1010848