A research team led by Professor Ouyang Songying from the School of Life Sciences at Fujian Normal University (FJNU) has made a significant breakthrough in understanding the pathogenesis of Legionella pneumophila, the bacterium responsible for Legionnaires' disease. Their latest study, which elucidates the catalytic mechanism of a novel actin-dependent phosphoryl-AMPylase, has been published in the high-impact journal Nature Chemical Biology on June 30.
Legionella pneumophila infects pulmonary macrophages and forms specialized membrane-bound vacuoles to survive and replicate within host cells. It employs effector proteins of the SidE family to carry out a non-canonical ubiquitination process that bypasses conventional E1 and E2 enzymes, promoting vacuole maturation. This process produces cytotoxic phosphoribosylated ubiquitin (PR-Ub), which is regulated by de-modifying effectors DupA/B.
Building on last year’s collaborative work with Professor Zhao-Qing Luo from Purdue University—which revealed how Legionella maintains ubiquitin homeostasis via the effector proteins LnaB and MavL—Prof. Ouyang’s team has now uncovered how LnaB acts as an actin-dependent phosphoryl-AMPylase. The enzyme catalyzes the AMPylation of PR-Ub to generate ADPR-Ub. By resolving a series of complex structures of LnaB, the team detailed the molecular mechanism through which host actin activates LnaB to drive the phosphoribosyl-AMPylation reaction.
This research not only reveals a new enzymatic catalytic mechanism and enhances the fundamental understanding of enzyme functionality, but also provides deeper insights into Legionella’s infection tactics. Moreover, it lays a groundwork for future studies on SHxxxE family toxins and offers a critical theoretical foundation for developing new anti-infective drugs.
The paper, entitled "Structure and mechanism of an actin-dependent bacterial phosphoryl-AMPylase," is published with FJNU as the primary affiliation. Co-first authors include FJNU Associate Professor Chen Taotao and doctoral candidates Lu Qiuhua and Zheng Siru. Professors Ouyang Songying (FJNU) and Zhao-Qing Luo (Purdue University) are co-corresponding authors. The collaborative effort also involved the team of Professor Jiaqi Fu from the First Hospital of Jilin University, with additional support from Professor Jinyu Li (Fuzhou University) and Professor Shan Li (Southern University of Science and Technology).
Link to the article: https://doi.org/10.1038/s41589-025-01945-w