Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX

Structure. 2009 Aug 12;17(8):1104-16. doi: 10.1016/j.str.2009.06.010.

Abstract

Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data and crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Catalysis
  • Crystallization
  • Crystallography, X-Ray
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / chemistry
  • Cyclic GMP / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Models, Biological
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Multimerization
  • Protein Structure, Tertiary*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • Bacterial Proteins
  • Receptors, Cell Surface
  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP

Associated data

  • PDB/3HV8
  • PDB/3HV9
  • PDB/3HVA
  • PDB/3HVB