PXD034922-1

PXD034922 is an original dataset announced via ProteomeXchange.

Title	Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-07-28
AnnouncementXML	Submission_2023-07-28_08:15:32.710.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	GuillaumeCHEVREUX
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-26 07:48:12	ID requested
⏵ 1	2023-07-28 08:15:33	announced
2	2023-11-14 06:48:26	announced	2023-11-14: Updated project metadata.

submitter keyword: N-terminal acetyltransferases,Immunoprecipitation, NatC, NatB, S. cerevisiae, NatA, Selective Translating Ribosomes, Affinity Purification

MathildeGarcia
contact affiliation	Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, UMR 7238, Laboratoire de Biologie Computationnelle et Quantitative, Paris, France
contact email	mathilde.garcia@sorbonne-universite.fr
lab head
GuillaumeCHEVREUX
contact affiliation	Institut Jacques Monod, CNRS UMR7592
contact email	guillaume.chevreux@ijm.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD034922

PRIDE project URI

• PRIDE
  1. PXD034922
     1. Label: PRIDE project
     2. Name: Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import