PXD054016-1

PXD054016 is an original dataset announced via ProteomeXchange.

Title	Genesis and regulation of C-terminal cyclic imides from protein damage
Description	C-Terminal cyclic imides are post-translational modifications (PTMs) that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that this class of aging-related modifications requires cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail. Here, we characterize the primary and secondary structures of peptides and proteins that promote intrinsic formation of C-terminal cyclic imides in comparison to deamidation, a related form of protein damage. Extrinsic effects from solution properties and stressors on the cellular proteome additionally promote C-terminal cyclic imide formation on proteins like glutathione synthetase (GSS) that are susceptible to aggregation if they are not removed by CRBN. This systematic investigation provides insight to the regions of the proteome that are prone to these unexpectedly frequent modifications, the effects of this form of protein damage on the protein stability, and the biological role of CRBN.
HostingRepository	PRIDE
AnnounceDate	2024-08-08
AnnouncementXML	Submission_2024-08-08_02:36:22.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Woo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-17 08:24:34	ID requested
⏵ 1	2024-08-08 02:36:22	announced
2	2024-10-22 06:52:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: protein cleavage, cyclic imide, cereblon, protein damage,post-translational modifications, deamidation

Christina Woo
contact affiliation	Department of Chemistry and Chemical Biology, Harvard University
contact email	cwoo@chemistry.harvard.edu
lab head
Christina Woo
contact affiliation	Harvard University
contact email	cwoo@chemistry.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054016
     1. Label: PRIDE project
     2. Name: Genesis and regulation of C-terminal cyclic imides from protein damage