PXD055898-1

PXD055898 is an original dataset announced via ProteomeXchange.

Title	Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit
Description	The integrated stress response (ISR) is a central signalling network that enables eukaryotic cells to respond to a variety of different environmental stresses. Such stresses cause ribosome collisions that lead to activation of the kinase Gcn2, resulting in the phosphorylation and inactivation of eukaryotic initiation factor 2 and thereby promoting selective translation of mRNAs to restore homeostasis. Despite the importance of the ISR and intensive study over the past decades, structural insight into how Gcn2 interacts with ribosomal particles has been lacking. Using ex vivo affinity purification approaches, we have obtained a native structure of a Gcn2 dimer in complex with the ribosomal 60S subunit. The Gcn2 dimer is formed by dimerization of the histidine tRNA synthetase-like domains, which establish extensive interactions with the stalk-base and sarcin-ricin loop of the 60S subunit. The C-terminal domain of Gcn2 is also dimerized and occupies the A- and P-site tRNA binding sites at the peptidyl-transferase center of the 60S subunit. Complementary functional studies indicate that binding of Gcn2 to the 60S subunit does not require the co-activators Gcn1 or Gcn20, nor does it lead to phosphorylation of eIF2a. Rather, upon stress, we observe a shift of Gcn2 from the 60S subunit into the colliding ribosome fraction, suggesting that the Gcn2-60S complex represents an inactive stand-by state to enable a rapid redistribution to collided ribosomes, and thereby facilitating a quick and efficient response to stress.
HostingRepository	PRIDE
AnnounceDate	2024-09-16
AnnouncementXML	Submission_2024-09-16_07:05:51.011.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tanel Tenson
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-16 06:51:07	ID requested
⏵ 1	2024-09-16 07:05:51	announced
2	2024-10-22 06:58:26	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: ribosome, cryoEM

Tanel Tenson
contact affiliation	Institute of Technology, University of Tartu, Tartu 50411, Estonia
contact email	tanel.tenson@ut.ee
lab head
Tanel Tenson
contact affiliation	University of Tartu
contact email	tanel.tenson@ut.ee
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055898
     1. Label: PRIDE project
     2. Name: Structure of a Gcn2 dimer in complex with the large 60S ribosomal subunit