title: The Caenorhabditis elegans Protein FIC-1 Is an AMPylase That Covalently Modifies Heat-Shock 70 Family Proteins, Translation Elongation Factors and Histones.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Truttmann
authors.affiliation: Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Victor E
authors.identifier: 0000-0001-5338-0973
authors.initials: VE
authors.lastname: Cruz
authors.affiliation: Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Xuanzong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Christoph
authors.initials: C
authors.lastname: Engert
authors.affiliation: Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Schwartz
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.|Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America.
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D009713:Nucleotidyltransferases / Q000235:genetics*; D010441:Peptide Chain Elongation, Translational; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D006657:Histones; D008565:Membrane Proteins; D011994:Recombinant Proteins; C000619111:FIC-1 protein, C elegans; C541422:FICD protein, human; D009713:Nucleotidyltransferases