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

Journal Article · · PLoS Genetics
 [1]; ORCiD logo [2];  [2];  [2];  [2];  [3];  [4]
  1. Whitehead Inst. for Biomedical Research, Cambridge, MA (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  3. Whitehead Inst. for Biomedical Research, Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  4. Genentech, South San Francisco, CA (United States)

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Inst. of Health
Grant/Contract Number:
P41 GM103403
OSTI ID:
1426270
Journal Information:
PLoS Genetics, Vol. 12, Issue 5; ISSN 1553-7404
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 29 works
Citation information provided by
Web of Science

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Cited By (14)

An oligomeric state-dependent switch in the ER enzyme FICD regulates AMPylation and deAMPylation of BiP. text January 2019
Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides journal May 2018
FIC proteins: from bacteria to humans and back again journal February 2018
Fic‐mediated deAMPylation is not dependent on homo‐dimerization and rescues toxic AMPylation in flies journal April 2018
An oligomeric state-dependent switch in FICD regulates AMPylation and deAMPylation of the chaperone BiP posted_content April 2019
An oligomeric state‐dependent switch in the ER enzyme FICD regulates AMP ylation and de AMP ylation of BiP journal September 2019
Adaptation to constant light requires Fic-mediated AMPylation of BiP to protect against reversible photoreceptor degeneration journal July 2018
Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies journal February 2018
Oligomerization of Hsp70: Current Perspectives on Regulation and Function journal September 2019
Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies journal October 2017
CryoAPEX - an electron tomography tool for subcellular localization of membrane proteins journal January 2019
Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides posted_content September 2017
Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors journal March 2018
CryoAPEX – an electron tomography tool for subcellular localization of membrane proteins journal March 2019