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AMPylation of small GTPases by Fic enzymes

Burak Gulen1,2, Amanda Casey1,2, Kim Orth1,2,3

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

FEBS Letters
|October 14, 2022
PubMed

Insights

Pathogens hijack host cell signaling by using AMPylation, a modification that disrupts small GTPase function. This review covers how filamentation induced by cyclic-AMP (Fic) domain enzymes mediate this process, impacting cellular pathways during infection.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Pathogen-Host Interactions

Background:

  • Small GTPases are crucial regulators of cellular pathways, functioning as molecular switches.
  • Pathogens frequently target host GTPase signaling networks during infection.
  • Post-translational modifications (PTMs) are key mechanisms used by pathogens to manipulate host cells.

Purpose of the Study:

  • To provide an overview of Fic-mediated AMPylation of small GTPases by pathogens.
  • To discuss related PTMs catalyzed by Fic enzymes on GTPases.
  • To highlight the role of AMPylation in pathogen-induced hijacking of host cellular processes.

Main Methods:

  • Literature review of studies on Fic enzymes and GTPase modification.
  • Analysis of the mechanisms of AMPylation and its impact on GTPase function.
  • Examination of pathogen strategies involving GTPase manipulation.

Main Results:

  • AMPylation, catalyzed by Fic domain enzymes, is a common PTM used by pathogens to target small GTPases.
  • AMPylation of small GTPases by pathogens results in their insensitivity to upstream regulation.
  • This modification leads to uncontrolled downstream effector activity, disrupting host cellular functions.

Conclusions:

  • Fic-mediated AMPylation represents a significant strategy employed by pathogens to subvert host GTPase signaling.
  • Understanding these modifications is crucial for developing strategies against infectious diseases.
  • Further research into Fic enzyme activity and GTPase regulation is warranted.
Keywords:
AMPylationFic enzymespost-translational modificationssmall GTPases

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