title: The structural basis of cyclic diguanylate signal transduction by PilZ domains.
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.
authors.affiliation: Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA.
authors.forename: Jordi
authors.initials: J
authors.lastname: Benach
authors.forename: Swarup S
authors.initials: SS
authors.lastname: Swaminathan
authors.forename: Rita
authors.initials: R
authors.lastname: Tamayo
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Handelman
authors.forename: Ewa
authors.initials: E
authors.lastname: Folta-Stogniew
authors.forename: John E
authors.initials: JE
authors.lastname: Ramos
authors.forename: Farhad
authors.initials: F
authors.lastname: Forouhar
authors.forename: Helen
authors.initials: H
authors.lastname: Neely
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Seetharaman
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D014734:Vibrio cholerae / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP