PXD048776

PXD048776 is an original dataset announced via ProteomeXchange.

Title	Formylation facilitates the reduction of oxidized initiator methionines
Description	Within a cell, protein-bound methionines can be oxidized by reactive oxygen species (ROS) or monooxygenases, and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation can result in structural damage or be the basis of functional regulation of enzymes. In addition to participating in redox reactions, methionines play an important role as the initial residue of translated proteins where they are commonly modified at their α-amine group by formylation or acetylation. Here, we investigated how formylation and acetylation of initiator methionines impact their propensity for oxidation and reduction. We show that in vitro, N-terminal methionine residues are particularly prone to chemical oxidation, and that their modification by formylation or acetylation greatly enhances their subsequent enzymatic reduction by MsrA and MsrB. Concordantly, in vivo ablation of methionyl-tRNA formyltransferase (MTF) in E. coli increases the prevalence of oxidized methionines within synthesized proteins. We show that oxidation of formylated initiator methionines is detrimental in part because it obstructs their ensuing de-formylation by peptide deformylase (PDF) and hydrolysis by methionyl aminopeptidase (MAP). Thus, by facilitating their reduction, formylation mitigates the misprocessing of oxidized initiator methionines.
HostingRepository	PRIDE
AnnounceDate	2024-11-06
AnnouncementXML	Submission_2024-11-05_22:30:21.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruiyue Tan
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	acetylated residue; monohydroxylated residue; formylated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-22 14:03:18	ID requested
⏵ 1	2024-11-05 22:30:21	announced

10.1073/PNAS.2403880121;

submitter keyword: N-Formylation

Methionine sulfoxide reductase (Msr)

Proteomics

Mass spectrometry (MS)

Methionine oxidation

Sina Ghaemmaghami
contact affiliation	Ghaemmaghami lab, Biology department, University of Rochester
contact email	sina.ghaemmaghami@rochester.edu
lab head
Ruiyue Tan
contact affiliation	University of Rochester
contact email	rtan12@ur.rochester.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048776
     1. Label: PRIDE project
     2. Name: Formylation facilitates the reduction of oxidized initiator methionines