The structural basis of cyclic diguanylate signal transduction by PilZ domains

Jordi Benach, Swarup S. Swaminathan, Rita Tamayo, Samuel K. Handelman, Ewa Folta-Stogniew, John E. Ramos, Farhad Forouhar, Helen Neely, Jayaraman Seetharaman, Andrew Camilli, John F. Hunt

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

The second messenger cyclic diguanylate (c-di-GMP) controls the transition between motile and sessile growth in eubacteria, but little is known about the proteins that sense its concentration. Bioinformatics analyses suggested that PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have determined a 1.9 Å crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ domain-containing protein from Vibrio cholerae. Either this protein or another specific PilZ domain-containing protein is required for V. cholerae to efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an N-terminal domain with a similar β-barrel fold. C-di-GMP contacts seven of the nine strongly conserved residues in the PilZ domain, including three in a seven-residue long N-terminal loop that undergoes a conformational switch as it wraps around c-di-GMP. This switch brings the PilZ domain into close apposition with the N-terminal domain, forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface. The very small size of the N-terminal conformational switch is likely to explain the facile evolutionary diversification of the PilZ domain.

Original languageEnglish (US)
Pages (from-to)5153-5166
Number of pages14
JournalEMBO Journal
Volume26
Issue number24
DOIs
StatePublished - Dec 12 2007
Externally publishedYes

Keywords

  • Allostery
  • Bacterial pathogenesis
  • Cyclic diguanylate (cyclic-di-GMP)
  • Fluorescence resonance energy transfer
  • X-ray crystallography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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