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.
MeSH terms
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Animals
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Caenorhabditis elegans / chemistry
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / microbiology
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Caenorhabditis elegans Proteins / genetics*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Crystallography, X-Ray
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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HSP70 Heat-Shock Proteins / chemistry
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Heat-Shock Response / genetics
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Histones / genetics
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Histones / metabolism
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Humans
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Immunity, Innate / genetics
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Nucleotidyltransferases / genetics*
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Peptide Chain Elongation, Translational*
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Protein Conformation
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Pseudomonas aeruginosa / genetics
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Pseudomonas aeruginosa / pathogenicity
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics*
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Recombinant Proteins / metabolism
Substances
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Caenorhabditis elegans Proteins
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Carrier Proteins
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DNA-Binding Proteins
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HSP70 Heat-Shock Proteins
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Histones
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Membrane Proteins
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Recombinant Proteins
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FIC-1 protein, C elegans
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FICD protein, human
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Nucleotidyltransferases