PXD040330-2

PXD040330 is an original dataset announced via ProteomeXchange.

Title	The DNA-binding induced (de)AMPylation activity of a Coxiella burnetii Fic enzyme targets Histone H3
Description	Intracellular bacterial pathogens such as Coxiella burnetii evade their host's immune response by secreting effector proteins that bind and modify host proteins, thereby reshaping cell signaling pathways that help establish a replication-friendly niche. Previous research has identified Filamentation induced by cyclic AMP (Fic) enzymes as effector proteins in bacterial infections that modify their target proteins via the post-translational modification AMPylation. Fic enzymes use adenosine triphosphate (ATP) as co-substrate to transfer the adenosine monophosphate (AMP) group to a hydroxyl-containing side chain of their target protein. Many representatives of this enzyme class contain an autoinhibitory helix that suppresses AMPylation activity in vitro by contacting the active site. The mechanisms reversing this inhibition are incompletely understood. Extensive studies of the only human Fic protein FICD have revealed that FICD can switch between AMPylation and the reversal of this modification, deAMPylation, by a monomer-dimer transition. However, so far FICD remained the only example where deAMPylation by dimerization could be shown. Here we identify the protein product of C. burnetii CBU_0822, termed C. burnetii Fic 2 (CbFic2), to AMPylate host cell histone H3 at S10 and S28. We show that CbFic2 is a bifunctional enzyme, both capable of AMPylation as well as deAMPylation, and is regulated by the binding of DNA via its C-terminal helix-turn-helix domain. We propose that CbFic2 is capable of AMPylation in its monomeric form, and that binding to DNA induces a deAMPylating dimer.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:26:09.880.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannah Voß
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Coxiella burnetii cb109; NCBI TaxID: 1196327;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-22 10:16:29	ID requested
1	2024-01-26 07:24:12	announced
⏵ 2	2024-10-22 06:26:12	announced	2024-10-22: Updated project metadata.

H, ö, pfner D, Cichy A, Pogenberg V, Krisp C, Mezouar S, Bach NC, Grotheer J, Zarza SM, Martinez E, Bonazzi M, Feige MJ, Sieber SA, Schl, ü, ter H, Itzen A, The DNA-binding induced (de)AMPylation activity of a Coxiella burnetii Fic enzyme targets Histone H3. Commun Biol, 6(1):1124(2023) [pubmed]

10.1038/s42003-023-05494-7;

submitter keyword: AMPylation, Histone H3, Fic enzyme, DNA-binding,Coxiella burnetii

Aymelt Itzen
contact affiliation	Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246 Hamburg, Germany
contact email	a.itzen@uke.de
lab head
Hannah Voß
contact affiliation	University Medical Center Hamburg Eppendorf, Institute of Clinical Chemistry and Laboratory Medicine, Group of Mass Spectrometric Proteomics
contact email	ha.voss@uke.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040330
     1. Label: PRIDE project
     2. Name: The DNA-binding induced (de)AMPylation activity of a Coxiella burnetii Fic enzyme targets Histone H3