4.5 Article

AMPylation of small GTPases by Fic enzymes

Journal

FEBS LETTERS
Volume 597, Issue 6, Pages 883-891

Publisher

WILEY
DOI: 10.1002/1873-3468.14516

Keywords

AMPylation; Fic enzymes; post-translational modifications; small GTPases

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Small GTPases play crucial roles in cellular pathways and are targeted by pathogens during infection. AMPylation, a common post-translational modification, is utilized by pathogens to hijack GTPase signaling. Understanding the AMPylation of small GTPases by pathogens contributes to the understanding of cellular infection mechanisms.
Small GTPases orchestrate numerous cellular pathways, acting as molecular switches and regulatory hubs to transmit molecular signals and because of this, they are often the target of pathogens. During infection, pathogens manipulate host cellular networks using post-translational modifications (PTMs). AMPylation, the modification of proteins with AMP, has been identified as a common PTM utilized by pathogens to hijack GTPase signalling during infection. AMPylation is primarily carried out by enzymes with a filamentation induced by cyclic-AMP (Fic) domain. Modification of small GTPases by AMP renders GTPases impervious to upstream regulatory inputs, resulting in unregulated downstream effector outputs for host cellular processes. Here, we overview Fic-mediated AMPylation of small GTPases by pathogens and other related PTMs catalysed by Fic enzymes on GTPases.

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