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bioRxiv · 10.64898/2026.07.09.737422

The Shewanella oneidensis Fic enzyme SoFic targets the switch-Iregion of EF-Tu for AMPylation

Runge, S.·Pogenberg, V.·Baumgart, A.·Siebels, B.·Schlueter, H.·Hecht-Bucher, M.·Itzen, A.
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Abstract

Fic enzymes mediate diverse post-translational modifications, including adenosine monophosphate (AMP) transfer and removal, referred to as AMPylation and deAMPylation, respectively. We identified the prokaryotic translation elongation factor Tu (EF-Tu) as an AMPylation target of the Fic enzyme SoFic. SoFic can constitutively reverse EF-Tu modification via deAMPylation whereas AMPylation depends on SoFic homodimerization. The complex crystal structure between SoFic and EF-Tu confirms a conserved target binding mode across evolutionary distant Fic enzymes. AMPylation disrupts EF-Tus regulatory switch-I region, causing translational inhibition. SoFic furthermore binds to its promotor DNA, suggesting a dual function as transcriptional and translational regulator in bacterial cells. Together, our structural and biochemical data provide valuable insights into the functional and regulatory diversity of Fic enzymes.

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Runge, S., Pogenberg, V., Baumgart, A., Siebels, B., Schlueter, H., Hecht-Bucher, M., Itzen, A.. 2026-07-10. The Shewanella oneidensis Fic enzyme SoFic targets the switch-Iregion of EF-Tu for AMPylation. https://doi.org/10.64898/2026.07.09.737422

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