Abstract

Pathogenic bacterium Legionella pneumophila , the causative agent of Legionnaires’ disease, secretes hundreds of effectors into host cells that subvert cell pathways during pathogenesis. The Lgt family effectors, containing Lgt1, Lgt2, and Lgt3, from L. pneumophila are glycosyltransferase that shut down protein synthesis in human cells by specific glycosylation of a serine residue in the eukaryotic elongation factor 1 A (eEF1A), but the action mechanism remains poorly understood. Herein, the structural basis of the action mechanism is unveiled. Lgt family effectors catalyze the transfer of glucose moiety of UDP-glucose in a conserved retaining mechanism, but exhibit different substrate recognition mechanisms. Lgt2 bears the positive-charged catalytic cleft to interact with the negatively charged patches in helices α 2 and α3 of eEF1A; instead, Lgt1 employs a negatively charged surface of E445 and E446, which are proposed to interact with residue Lys51 in eEF1A. And Lgt family effectors inhibit host unfolded protein response by shutting down host protein synthesis. These results provide a structural basis of action mechanism of glycosyltransferase and highlight the role of glycosyltransferase in Legionella 's lifecycle.