Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246, Hamburg, Germany.
Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Group of Proteinchemistry, Technical University of Munich, Lichtenbergstraße 4, 85747, Garching, Germany.
Commun Biol. 2023 Nov 6;6(1):1124. doi: 10.1038/s42003-023-05494-7.
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, termed C. burnetii Fic 2 (CbFic2), to AMPylate host cell histone H3 at serine 10 and serine 28. We show that CbFic2 acts as a bifunctional enzyme, both capable of AMPylation as well as deAMPylation, and is regulated by the binding of DNA via a C-terminal helix-turn-helix domain. We propose that CbFic2 performs AMPylation in its monomeric state, switching to a deAMPylating dimer upon DNA binding. This study unveils reversible histone modification by a specific enzyme of a pathogenic bacterium.
细胞内细菌病原体柯克斯体通过分泌效应蛋白来逃避宿主反应，这些效应蛋白有助于建立一个有利于复制的小生境。环腺苷酸 (cAMP) 诱导的细菌丝状化 (Fic) 酶可以通过将腺苷单磷酸 (AMP) 从三磷酸腺苷 (ATP) 转移到含有羟基的侧链上来共价修饰靶蛋白，从而作为效应蛋白发挥作用，对靶蛋白进行翻译后 AMP 化。在这里，我们鉴定了柯克斯体 CBU_0822 的基因产物，称为柯克斯体 Fic2 (CbFic2)，它可以使宿主细胞组蛋白 H3 的丝氨酸 10 和丝氨酸 28 发生 AMP 化。我们表明，CbFic2 是一种双功能酶，既能进行 AMP 化，也能进行去 AMP 化，并通过 C 末端螺旋-转角-螺旋结构域与 DNA 结合来调节。我们提出 CbFic2 在其单体状态下进行 AMP 化，在与 DNA 结合时切换为去 AMP 化二聚体。本研究揭示了一种致病性细菌中特定酶的可逆组蛋白修饰。
