Affiliation:
1. Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation The Key Laboratory of Innate Immune Biology of Fujian Province Biomedical Research Center of South China Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education College of Life Sciences Fujian Normal University Fuzhou 350117 China
2. Department of Virology School of Public Health Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China
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 α2 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.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Subject
General Earth and Planetary Sciences,General Environmental Science