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The structural basis of cyclic diguanylate signal transduction by PilZ domains
Author(s) -
Benach Jordi,
Swaminathan Swarup S,
Tamayo Rita,
Handelman Samuel K,
FoltaStogniew Ewa,
Ramos John E,
Forouhar Farhad,
Neely Helen,
Seetharaman Jayaraman,
Camilli Andrew,
Hunt John F
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601918
Subject(s) - biology , signal transduction , transduction (biophysics) , microbiology and biotechnology , computational biology , botany
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.