Download MendeleyThe structural basis of cyclic diguanylate signal transduction by PilZ domains.
Benach, J., Swaminathan, S.S., Tamayo, R., Handelman, S.K., Folta-Stogniew, E., Ramos, J.E., Forouhar, F., Neely, H., Seetharaman, J., Camilli, A., Hunt, J.F.(2007) EMBO J 26: 5153-5166
- PubMed: 18034161
- DOI: https://doi.org/10.1038/sj.emboj.7601918
- Primary Citation of Related Structures:
2RDE - PubMed 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 A 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 beta-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.
Organizational Affiliation:
Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA.
