PXD050224 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses in bacterial pneumonia |
Description | The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. Here We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets DARS2 for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with a robust increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory properties which extended DARS2 lifespan in cells. The results suggest we show a unique biological role for an extracellular, mitochondrially derived enzyme and its molecular control regulated by the ubiquitin apparatus, which may serve as a mechanistic platform to enhance protective host immunity through small molecule discovery. |
HostingRepository | PRIDE |
AnnounceDate | 2024-08-10 |
AnnouncementXML | Submission_2024-08-10_12:04:27.177.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Benjamin Johnson |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitination signature dipeptidyl lysine; acetylated residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-28 13:23:54 | ID requested | |
⏵ 1 | 2024-08-10 12:04:28 | announced | |
Publication List
10.1038/s41467-024-50031-7; |
Johnson BS, Farkas D, El-Mergawy R, Adair JA, Elhance A, Eltobgy M, Coan FM, Chafin L, Joseph JA, Cornwell A, Johns FJ, Rosas L, Rojas M, Farkas L, Bednash JS, Londino JD, Ray P, Ray A, Kagan V, Lee JS, Chen BB, Mallampalli RK, Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses. Nat Commun, 15(1):6172(2024) [pubmed] |
Keyword List
submitter keyword: inflammation, pneumonia,DARS2 |
Contact List
Rama K Mallampalli |
contact affiliation | S. Robert Davis Chair of Medicine Professor and Chair, Department of Internal Medicine Director, Medical Scientist Training Program |
contact email | Rama.Mallampalli2@osumc.edu |
lab head | |
Benjamin Johnson |
contact affiliation | The Ohio State University |
contact email | benjamin.johnson@osumc.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050224
- Label: PRIDE project
- Name: Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses in bacterial pneumonia