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