Nucleotide signaling pathway convergence in a cAMP-sensing bacterial c-di-GMP phosphodiesterase.

Research output: Contribution to journalArticlepeer-review

Authors

  • Sarah M Basford
  • Ruth Nottingham
  • Rebecca Lowry
  • Carey Lambert
  • Matthew Tridgett
  • Rob Till
  • Rashidah Ahmad
  • Rowena Fung
  • Laura Hobley
  • William S Hughes
  • R. Elizabeth Sockett

Colleges, School and Institutes

Abstract

Bacterial usage of the cyclic dinucleotide c-di-GMP is widespread, governing the transition between motile/sessile and unicellular/multicellular behaviors. There is limited information on c-di-GMP metabolism, particularly on regulatory mechanisms governing control of EAL c-di-GMP phosphodiesterases. Herein, we provide high-resolution structures for an EAL enzyme Bd1971, from the predatory bacterium Bdellovibrio bacteriovorus, which is controlled by a second signaling nucleotide, cAMP. The full-length cAMP-bound form reveals the sensory N-terminus to be a domain-swapped variant of the cNMP/CRP family, which in the cAMP-activated state holds the C-terminal EAL enzyme in a phosphodiesterase-active conformation. Using a truncation mutant, we trap both a half-occupied and inactive apo-form of the protein, demonstrating a series of conformational changes that alter juxtaposition of the sensory domains. We show that Bd1971 interacts with several GGDEF proteins (c-di-GMP producers), but mutants of Bd1971 do not share the discrete phenotypes of GGDEF mutants, instead having an elevated level of c-di-GMP, suggesting that the role of Bd1971 is to moderate these levels, allowing "action potentials" to be generated by each GGDEF protein to effect their specific functions.

Bibliographic note

© 2019 The Authors. Published under the terms of the CC BY 4.0 license.

Details

Original languageEnglish
Article numbere100772
Number of pages19
JournalThe EMBO journal
Volume38
Issue number15
Publication statusPublished - 29 Jul 2019

Keywords

  • bacterial signaling, Bdellovibrio, cAMP, Cyclic-di-GMP, EAL domain