The Caenorhabditis elegans Protein FIC-1 Is an AMPylase That Covalently Modifies Heat-Shock 70 Family Proteins, Translation Elongation Factors and Histones

• Published in: PLoS genetics 2016-05, Vol.12 (5), p.e1006023-e1006023
• Main Authors: Truttmann, Matthias C, Cruz, Victor E, Guo, Xuanzong, Engert, Christoph, Schwartz, Thomas U, Ploegh, Hidde L
• Format: Article
• Language: English
• Subjects: Animals; autoradiography; BASIC BIOLOGICAL SCIENCES; Biology and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - chemistry; Caenorhabditis elegans - genetics; Caenorhabditis elegans - microbiology; Caenorhabditis elegans Proteins - genetics; Carrier Proteins - chemistry; Carrier Proteins - genetics; Crystallography, X-Ray; Data collection; DNA-binding proteins; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; elongation factors; Genes; Genetic aspects; Heat shock proteins; heat shock response; Heat-Shock Response - genetics; histones; Histones - genetics; Histones - metabolism; HSP70 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; Immunity, Innate - genetics; Insects; Mass spectrometry; Medicine and Health Sciences; Membrane Proteins - chemistry; Membrane Proteins - genetics; Nematodes; Nucleotidyltransferases - genetics; Observations; Peptide Chain Elongation, Translational; Physiological aspects; Protein Conformation; protein translation; Proteins; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Research and Analysis Methods; Scientific imaging; Studies; Translation (Genetics)
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006023

Protein AMPylation by Fic domain-containing proteins (Fic proteins) is an ancient and conserved post-translational modification of mostly unexplored significance. Here we characterize the Caenorhabditis elegans Fic protein FIC-1 in vitro and in vivo. FIC-1 is an AMPylase that localizes to the nuclear surface and modifies core histones H2 and H3 as well as heat shock protein 70 family members and translation elongation factors. The three-dimensional structure of FIC-1 is similar to that of its human ortholog, HYPE, with 38% sequence identity. We identify a link between FIC-1-mediated AMPylation and susceptibility to the pathogen Pseudomonas aeruginosa, establishing a connection between AMPylation and innate immunity in C. elegans.