PXD049090

PXD049090 is an original dataset announced via ProteomeXchange.

Title	The HisRS-like domain of GCN2 is a pseudoenzyme that can bind uncharged tRNA - HX-MS Data
Description	GCN2 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.
HostingRepository	PRIDE
AnnounceDate	2024-02-01
AnnouncementXML	Submission_2024-02-01_12:32:58.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frantisek Filandr
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-01 11:56:31	ID requested
⏵ 1	2024-02-01 12:32:58	announced

Dataset with its publication pending

submitter keyword: HDX-MS

David Schriemer
contact affiliation	Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary
contact email	dschriem@ucalgary.ca
lab head
Frantisek Filandr
contact affiliation	Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary
contact email	frantisek.filandr@ucalgary.ca
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/2024/02/PXD049090

PRIDE project URI

• PRIDE
  1. PXD049090
     1. Label: PRIDE project
     2. Name: The HisRS-like domain of GCN2 is a pseudoenzyme that can bind uncharged tRNA - HX-MS Data