PXD030978

PXD030978 is an original dataset announced via ProteomeXchange.

Title	GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation endproducts
Description	Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetics approaches have attributed functions to proteins in established metabolic pathways limiting the possibility of identifying novel biology which may be relevant to human disease. We undertook a bottom-up biochemistry approach to identify evolutionarily conserved mitochondrial proteins with catalytic potential. Here, we identify a Parkinson-associated DJ-1/PARK7-like protein – glutamine amidotransferase-like class 1 domain containing 3A (GATD3A), with evolutionary origins from gammaproteobacteria. We demonstrate that GATD3A localizes to the mitochondrial matrix and functions as a deglycase. Through its amidolysis domain, GATD3A removes non-enzymatic chemical modifications produced during the Maillard reaction between dicarbonyls and amines of nucleotides and amino acids. GATD3A interacts with factors involved in mitochondrial mRNA processing and translation, suggestive of a role in maintaining integrity of important biomolecules through its deglycase activity. The loss of GATD3A in mice is associated with accumulation of advanced glycation endproducts (AGEs) and altered mitochondrial dynamics. An evolutionary perspective helped us prioritize a previously uncharacterized but predicted mitochondrial protein GATD3A, which mediates the removal of early glycation intermediates. GATD3A restricts the formation of AGEs in mitochondria and is a relevant target for diseases where AGE deposition is a pathological hallmark. This dataset consists of peptides identified following in-gel digestions of bands observed following FPLC purification of recombinant human GATD3A.
HostingRepository	PRIDE
AnnounceDate	2023-10-02
AnnouncementXML	Submission_2023-10-02_02:27:18.247.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AnandSwaroop
SpeciesList	scientific name: Escherichia coli (strain K12); NCBI TaxID: 83333; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-14 14:44:25	ID requested
1	2022-03-02 07:35:27	announced
⏵ 2	2023-10-02 02:27:19	announced	2023-10-02: Updated project metadata.

Smith AJ, Advani J, Brock DC, Nellissery J, Gumerson J, Dong L, Aravind L, Kennedy B, Swaroop A, GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products. BMC Biol, 20(1):68(2022) [pubmed]

submitter keyword: Glycation, advanced glycation endproduct, FPLC, glutamine amidotransferase, deglycase, DJ-1, mitochondria, molecular evolution, PARK7,in gel digestion

AnandSwaroop
contact affiliation	Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
contact email	swaroopa@nei.nih.gov
lab head
AnandSwaroop
contact affiliation	National Eye Institute, National Institutes of Health
contact email	swaroopa@nei.nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030978
     1. Label: PRIDE project
     2. Name: GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation endproducts