In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2023-8-16), p. e1010848-
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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010848
DOI:
10.1371/journal.pgen.1010848.g001
DOI:
10.1371/journal.pgen.1010848.g002
DOI:
10.1371/journal.pgen.1010848.g003
DOI:
10.1371/journal.pgen.1010848.g004
DOI:
10.1371/journal.pgen.1010848.g005
DOI:
10.1371/journal.pgen.1010848.g006
DOI:
10.1371/journal.pgen.1010848.s001
DOI:
10.1371/journal.pgen.1010848.s002
DOI:
10.1371/journal.pgen.1010848.s003
DOI:
10.1371/journal.pgen.1010848.s004
DOI:
10.1371/journal.pgen.1010848.s005
DOI:
10.1371/journal.pgen.1010848.s006
DOI:
10.1371/journal.pgen.1010848.s007
DOI:
10.1371/journal.pgen.1010848.s008
DOI:
10.1371/journal.pgen.1010848.s009
DOI:
10.1371/journal.pgen.1010848.s010
DOI:
10.1371/journal.pgen.1010848.s011
DOI:
10.1371/journal.pgen.1010848.s012
DOI:
10.1371/journal.pgen.1010848.s013
DOI:
10.1371/journal.pgen.1010848.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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