Dataset Information

The DNA-binding induced (de)AMPylation activity of a Coxiella burnetii Fic enzyme targets Histone H3

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Coxiella Burnetii Cb109

SUBMITTER: Hannah Voß

LAB HEAD: Aymelt Itzen

PROVIDER: PXD040330 | Pride | 2024-01-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	201016_CK_DH_THPI_CbFic2.msf	Msf
	201016_CK_DH_THPI_CbFic2_EG_1.raw	Raw
	201016_CK_DH_THPI_CbFic2_EG_2.raw	Raw
	201016_CK_DH_THPI_CbFic2_EG_3.raw	Raw
	201016_CK_DH_THPI_CbFic2_HA_1.raw	Raw

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The DNA-binding induced (de)AMPylation activity of a Coxiella burnetii Fic enzyme targets Histone H3.

Höpfner Dorothea D Cichy Adam A Pogenberg Vivian V Krisp Christoph C Mezouar Soraya S Bach Nina C NC Grotheer Jan J Zarza Sandra Madariaga SM Martinez Eric E Bonazzi Matteo M Feige Matthias J MJ Sieber Stephan A SA Schlüter Hartmut H Itzen Aymelt A

Communications biology 20231106 1

The intracellular bacterial pathogen Coxiella burnetii evades the host response by secreting effector proteins that aid in establishing a replication-friendly niche. Bacterial filamentation induced by cyclic AMP (Fic) enzymes can act as effectors by covalently modifying target proteins with the posttranslational AMPylation by transferring adenosine monophosphate (AMP) from adenosine triphosphate (ATP) to a hydroxyl-containing side chain. Here we identify the gene product of C. burnetii CBU_0822, ...[more]

PMID: 37932372

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