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PXD049090

PXD049090 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe HisRS-like domain of GCN2 is a pseudoenzyme that can bind uncharged tRNA - HX-MS Data
DescriptionGCN2 is a stress response kinase that phosphorylates the translation initiation factor eIF2to inhibit general protein synthesis when activated by uncharged tRNA and stalled ribosomes. The presence of a HisRS-like domain in GCN2, normally associated with the ability to bind and aminoacylate tRNAs, led to the hypothesis that eIF2 kinase activity is regulated by the direct binding of this domain to uncharged tRNA. Here we solved the structure of the HisRS-like domain in the context of full-length GCN2 by cryoEM. Structure and function analysis shows the HisRS-like domain of GCN2 has lost tRNA charging, ATP binding, and histidine binding activity but retains the ability to bind tRNA. Hydrogen deuterium exchange mass spectrometry (HX-MS), site-directed mutagenesis and computational docking experiments support a tRNA binding model that overlaps with but is partially shifted from that employed by bona fide HisRS enzymes. These results demonstrate that the HisRS-like domain of GCN2 is a pseudoenzyme and advance our understanding of GCN2 regulation and function.
HostingRepositoryPRIDE
AnnounceDate2024-02-01
AnnouncementXMLSubmission_2024-02-01_12:32:58.618.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrantisek Filandr
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-01 11:56:31ID requested
12024-02-01 12:32:58announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: HDX-MS
Contact List
David Schriemer
contact affiliationDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary
contact emaildschriem@ucalgary.ca
lab head
Frantisek Filandr
contact affiliationDepartment of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary
contact emailfrantisek.filandr@ucalgary.ca
dataset submitter
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Dataset FTP location
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