Structure and Regulation of EAL Domain Proteins

  • Dom Bellini
  • Andrew Hutchin
  • Odel Soren
  • Jeremy S. Webb
  • Ivo Tews
  • Martin A. WalshEmail author


The formation and dispersal of bacterial biofilms is strongly correlated with cellular levels of bis-(3′–5′) cyclic dimeric guanosine monophosphate, cyclic di-GMP, a secondary messenger that has been shown to be involved in regulation of a broad range of cellular processes in bacteria. Diguanylate cyclases (DGCs) are required for synthesis of cyclic di-GMP, with phosphodiesterases (PDEs) responsible for its breakdown. This review focuses on PDEs characterised by the presence of the conserved “EAL” sequence motif. Typically found in multi-domain proteins, EAL domains can couple to sensory or regulatory domains that allow their activity to be regulated by environmental stimuli or cellular cues. Additionally, catalytically inactive EAL PDEs are suggested to have a sensory or otherwise regulatory function. Recent structure determination provides a wealth of information on PDE function and regulation and has provided novel insight into the enzymatic reaction mechanism. Several regulatory layers may control activity, including dimerisation, active site formation, and metal coordination. In this review, we provide a concise summary of these exciting findings and highlight open research questions that will allow us in future to decipher many of the cellular signals responsible for regulation of PDE activity and cellular processes influenced by these pivotal enzymes.


Cyclic di-GMP signalling Phosphodiesterase EAL domain Bacterial biofilms Protein structure 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Dom Bellini
    • 1
    • 2
  • Andrew Hutchin
    • 3
  • Odel Soren
    • 4
  • Jeremy S. Webb
    • 4
  • Ivo Tews
    • 4
  • Martin A. Walsh
    • 5
    • 2
    Email author
  1. 1.School of Life SciencesUniversity of WarwickCoventryUK
  2. 2.Research Complex at Harwell, Harwell Science and Innovation CampusDidcot, OxfordshireUK
  3. 3.Structure and Function of Biological Membranes LabUniversité Libre de BruxellesBruxellesBelgium
  4. 4.Biological SciencesUniversity of SouthamptonSouthamptonUK
  5. 5.Diamond Light Source, Harwell Science and Innovation CampusDidcotUK

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