PXD022564
PXD022564 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs |
Description | Eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2), better known as PKR plays a key role in the response to viral infections and cellular homeostasis by regulating mRNA translation. Upon binding dsRNA, PKR is activated through homodimerization and subsequent autophosphorylation on Thr446 and Thr451 residues. In this study, we identified a novel PKR phosphorylation site, Ser6, located 3 aminoacids upstream the first double-stranded RNA binding domain (DRBM1). Another Ser residue occurs in PKR at position 97, the very same position relative to the DRBM2. Ser or Thr residues also occur 3 amino acids upstream DRBMs of other proteins such as ADAR1 or DICER. Phosphoinhibiting mutations (Ser-to-Ala) introduced at Ser6 and Ser97 spontaneously activated PKR. In contrast, phosphomimetic mutations (Ser-to-Asp) inhibited PKR activation following either poly (I:C) transfection or virus infection. These mutations moderately affected dsRNA binding, suggesting a model where negative charges occuring at position 6 and 97 tighten the interaction of DRBMs with the kinase domain, thus keeping PKR in an inactive, closed conformation even in the presence of dsRNA. This study provides new insights on PKR regulation mechanisms and identifies Ser6 and Ser97 as potential targets to modulate PKR activity for therapeutic purposes |
HostingRepository | PRIDE |
AnnounceDate | 2021-05-11 |
AnnouncementXML | Submission_2021-05-10_22:26:47.936.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD022564 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Didier Vertommen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | S-carboxamidoethyl-L-cysteine; phosphorylated residue; N-acetyl-L-methionine; monohydroxylated residue; mono N-acetylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2020-11-16 08:01:21 | ID requested | |
1 | 2021-05-10 00:28:55 | announced | |
2 | 2021-05-10 22:21:49 | announced | 2021-05-11: Updated project metadata. |
⏵ 3 | 2021-05-10 22:26:48 | announced | 2021-05-11: Updated project metadata. 2021-05-11: Updated publication reference for PubMed record(s): 33911136. 2021-05-11: Updated publication reference for DOI(s): 10.1038/S41598-021-88610-Z. |
Publication List
10.1038/S41598-021-88610-Z; |
Cesaro T, Hayashi Y, Borghese F, Vertommen D, Wavreil F, Michiels T, PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs. Sci Rep, 11(1):9188(2021) [pubmed] |
Keyword List
submitter keyword: dsRNA binding, viral infection,PKR, autophosphorylation, regulation |
Contact List
Thomas Michiels | |
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contact affiliation | Université Catholique de Louvain, de Duve Institute, VIRO B1.74.07, 74, avenue Hippocrate, B-1200, Brussels, Belgium |
contact email | thomas.michiels@uclouvain.be |
lab head | |
Didier Vertommen | |
contact affiliation | UCL - de Duve Institute, Brussels Belgium |
contact email | didier.vertommen@uclouvain.be |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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