PXD058390

PXD058390 is an original dataset announced via ProteomeXchange.

Title	Pausing protein acetylation by an Ac-CoA synthetase/acetyltransferase complex.
Description	Acetyl-CoA synthetase (Acs) generates acetyl-Coenzyme A (Ac-CoA) but its excessive activity can deplete ATP and lead to growth arrest. To prevent this, Acs is tightly regulated through Ac-CoA-dependent feedback inhibition executed by Ac-CoA-dependent acetyltransferases such as AcuA in Bacillus subtilis. AcuA acetylates the catalytic lysine of AcsA turning the synthetase inactive. Here we report an Ac-CoA independent inhibition mechanism of AcsA, which relies on a complex between AcsA and AcuA. Our structural analysis reveals that AcuA and AcsA form a tightly intertwined complex – the C-terminal domain binds to acetyltransferase domain of AcuA, while the C-terminus of AcuA occupies the CoA-binding site in the N-terminal domain of AcsA. Our structure-guided biochemical analysis reveals that AcuA inhibits AcsA by an Ac-CoA-independent inhibition via the AcsA-AcuA complex, in addition to the well-known Ac-CoA-dependent inhibition via acetylation of the catalytic lysine 549 in AcsA disrupting the complex. These findings elucidate how AcuA specifically binds to its target and inhibits activity through an unprecedented Ac-CoA-independent mechanism when Ac-CoA levels are low. Our study suggests that the two mechanistically distinct inhibitory mechanisms accomplished by AcuA adjust AcsA activity to the cellular concentrations of the different substrates of the reaction, illustrating the complexity underlying the regulatory framework of acetyl-CoA synthesis from acetate.
HostingRepository	PRIDE
AnnounceDate	2025-03-17
AnnouncementXML	Submission_2025-03-17_08:26:24.252.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wieland Steinchen
SpeciesList	scientific name: Bacillus subtilis subsp. subtilis str. 168; NCBI TaxID: 224308;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-28 12:00:19	ID requested
1	2025-02-28 07:44:45	announced
⏵ 2	2025-03-17 08:26:25	announced	2025-03-17: Updated project metadata.

10.1038/s41467-025-57842-2;

Zheng L, Du Y, Steinchen W, Girbig M, Abendroth F, Jalomo-Khayrova E, Bedrunka P, Bekeredjian-Ding I, Mais CN, Hochberg GKA, Freitag J, Bange G, Regulation of acetyl-CoA biosynthesis via an intertwined acetyl-CoA synthetase/acetyltransferase complex. Nat Commun, 16(1):2557(2025) [pubmed]

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: AcsA, cryo-EM,Protein acetylation, HDX-MS, AcuA

Gert Bange
contact affiliation	University Marburg, Center for Synthetic Microbiology (SYNMIKRO) & Department of Chemistry, Karl-von-Frisch Strasse 14, 35043 Marburg, Germany
contact email	bangeg@staff.uni-marburg.de
lab head
Wieland Steinchen
contact affiliation	Philipps-University Marburg, Department of Chemistry & SYNMIKRO, Karl-von-Frisch-Straße 14, 35043 Marburg, GERMANY
contact email	wieland.steinchen@synmikro.uni-marburg.de
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/2025/02/PXD058390

PRIDE project URI

• PRIDE
  1. PXD058390
     1. Label: PRIDE project
     2. Name: Pausing protein acetylation by an Ac-CoA synthetase/acetyltransferase complex.