PXD033787-1

PXD033787 is an original dataset announced via ProteomeXchange.

Title	Coenzyme A binding sites induce proximal acylation across protein families
Description	Lysine acylations, such as acetylation, succinylation, or glutarylation, are post-translational modifications that regulate protein function. In mitochondria, lysine acylation is predominantly non-enzymatic and only a specific subset of the proteome has been identified as acylated. Coenzyme A (CoA), a metabolite required in several metabolic pathways, can act as an acyl group carrier via a thioester bond. However, what controls the acylation of lysine residues in the mitochondria remains poorly understood. Using published datasets, we found that proteins with a CoA-binding site are more likely to be acetylated, succinylated, and glutarylated. Using computational modeling, we discovered that, in CoA-binding proteins, lysine residues near the CoA-binding pocket are more likely to be acylated than those far away from the CoA-binding pocket. We hypothesized that acyl-CoA binding enhances the acylation of nearby lysine residues. To experimentally test this hypothesis, we used enoyl-CoA hydratase short chain 1 (ECHS1), a mitochondrial protein with a CoA-binding pocket, and co-incubated ECHS1 with succinyl-CoA and CoA. Using mass spectrometry, we found that succinyl-CoA induced widespread lysine succinylation and that CoA competitively inhibited ECHS1 succinylation. In addition, CoA-induced inhibition at a particular lysine site was inversely correlated with the distance between this lysine residue and the CoA-binding pocket. This indicated that CoA acts as a competitive inhibitor of ECHS1 succinylation by binding to the CoA-binding pocket. Together, this study suggests proximal acylation at protein CoA-binding sites is a primary mechanism for lysine acylation in the mitochondria.
HostingRepository	MassIVE
AnnounceDate	2022-05-10
AnnouncementXML	Submission_2022-05-10_21:52:32.727.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joanna Bons
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	N6-succinyl-L-lysine
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-09 17:54:42	ID requested
⏵ 1	2022-05-10 21:52:33	announced

no publication

submitter keyword: Lysine acylation, CoA-binding site, Quantitative proteomics, Succinylation, Proximal acylation

Birgit Schilling
contact affiliation	Buck Institute
contact email	bschilling@buckinstitute.org
lab head
Joanna Bons
contact affiliation	Buck Institute for Research on Aging
contact email	jbons@buckinstitute.org
dataset submitter

MassIVE dataset URI

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