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

• Main Authors: Truttmann, Matthias (Contributor), Cruz, Victor Emmanuel (Contributor), Guo, Xuanzong (Contributor), Engert, Christoph (Contributor), Schwartz, Thomas (Contributor), Ploegh, Hidde (Contributor)
• Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
• Format: Article
• Language: English
• Published: Public Library of Science, 2016-12-09T19:51:39Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (P41 GM103403)
Swiss National Science Foundation (Advanced Postdoc Mobility Fellowship)
National Institutes of Health (U.S.) (NIH Pioneer Award (DP01))