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Signaling protein PDB id
3bre
Jmol
Contents
Protein chains
322 a.a. *
Ligands
C2E ×4
Metals
_MG ×2
* Residue conservation analysis
PDB id:
3bre
Name: Signaling protein
Title: Crystal structure of p.Aeruginosa pa3702
Structure: Probable two-component response regulator. Chain: a, b. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 208964. Strain: pao1. Gene: wspr. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.40Å     R-factor:   0.242     R-free:   0.278
Authors: N.De,M.Pirruccello,P.V.Krasteva,N.Bae,R.V.Raghavan,H.Sonderm
Key ref: N.De et al. (2008). Phosphorylation-independent regulation of the diguanylate cyclase WspR. Plos Biol, 6, e67. PubMed id: 18366254 DOI: 10.1371/journal.pbio.0060067
Date:
21-Dec-07     Release date:   01-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
A3LEF6  (A3LEF6_PSEAE) -  Putative uncharacterized protein
Seq:
Struc: 		347 a.a.
322 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     intracellular signal transduction   4 terms 
  Biochemical function     two-component response regulator activity     2 terms  

 

 
DOI no: 10.1371/journal.pbio.0060067 Plos Biol 6:e67 (2008)
PubMed id: 18366254  
 
 
Phosphorylation-independent regulation of the diguanylate cyclase WspR.
N.De, M.Pirruccello, P.V.Krasteva, N.Bae, R.V.Raghavan, H.Sondermann.
 
  ABSTRACT  
 
Environmental signals that trigger bacterial pathogenesis and biofilm formation are mediated by changes in the level of cyclic dimeric guanosine monophosphate (c-di-GMP), a unique eubacterial second messenger. Tight regulation of cellular c-di-GMP concentration is governed by diguanylate cyclases and phosphodiesterases, which are responsible for its production and degradation, respectively. Here, we present the crystal structure of the diguanylate cyclase WspR, a conserved GGDEF domain-containing response regulator in Gram-negative bacteria, bound to c-di-GMP at an inhibitory site. Biochemical analyses revealed that feedback regulation involves the formation of at least three distinct oligomeric states. By switching from an active to a product-inhibited dimer via a tetrameric assembly, WspR utilizes a novel mechanism for modulation of its activity through oligomerization. Moreover, our data suggest that these enzymes can be activated by phosphodiesterases. Thus, in addition to the canonical pathways via phosphorylation of the regulatory domains, both product and enzyme concentration contribute to the coordination of c-di-GMP signaling. A structural comparison reveals resemblance of the oligomeric states to assemblies of GAF domains, widely used regulatory domains in signaling molecules conserved from archaea to mammals, suggesting a similar mechanism of regulation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21275021 L.Zhang, and M.Meuwly (2011).
Stability and dynamics of cyclic diguanylic acid in solution.
  Chemphyschem, 12, 295-302.  
21304926 M.V.Navarro, P.D.Newell, P.V.Krasteva, D.Chatterjee, D.R.Madden, G.A.O'Toole, and H.Sondermann (2011).
Structural basis for c-di-GMP-mediated inside-out signaling controlling periplasmic proteolysis.
  PLoS Biol, 9, e1000588.
PDB codes: 3pjt 3pju 3pjv 3pjw 3pjx
19707751 D.Antoniani, P.Bocci, A.Maciag, N.Raffaelli, and P.Landini (2010).
Monitoring of diguanylate cyclase activity and of cyclic-di-GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors.
  Appl Microbiol Biotechnol, 85, 1095-1104.  
19901023 F.Rao, R.Y.See, D.Zhang, D.C.Toh, Q.Ji, and Z.X.Liang (2010).
YybT is a signaling protein that contains a cyclic dinucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity.
  J Biol Chem, 285, 473-482.  
20030712 J.C.Freedman, E.A.Rogers, J.L.Kostick, H.Zhang, R.Iyer, I.Schwartz, and R.T.Marconi (2010).
Identification and molecular characterization of a cyclic-di-GMP effector protein, PlzA (BB0733): additional evidence for the existence of a functional cyclic-di-GMP regulatory network in the Lyme disease spirochete, Borrelia burgdorferi.
  FEMS Immunol Med Microbiol, 58, 285-294.  
20300602 J.G.Malone, T.Jaeger, C.Spangler, D.Ritz, A.Spang, C.Arrieumerlou, V.Kaever, R.Landmann, and U.Jenal (2010).
YfiBNR mediates cyclic di-GMP dependent small colony variant formation and persistence in Pseudomonas aeruginosa.
  PLoS Pathog, 6, e1000804.  
20576684 L.Tagliabue, D.Antoniani, A.Maciag, P.Bocci, N.Raffaelli, and P.Landini (2010).
The diguanylate cyclase YddV controls production of the exopolysaccharide poly-N-acetylglucosamine (PNAG) through regulation of the PNAG biosynthetic pgaABCD operon.
  Microbiology, 156, 2901-2911.  
20226724 M.Y.Galperin (2010).
Diversity of structure and function of response regulator output domains.
  Curr Opin Microbiol, 13, 150-159.  
20467666 N.Liu, T.Pak, and E.M.Boon (2010).
Characterization of a diguanylate cyclase from Shewanella woodyi with cyclase and phosphodiesterase activities.
  Mol Biosyst, 6, 1561-1564.  
20165945 P.Landini, D.Antoniani, J.G.Burgess, and R.Nijland (2010).
Molecular mechanisms of compounds affecting bacterial biofilm formation and dispersal.
  Appl Microbiol Biotechnol, 86, 813-823.  
20080056 R.Gao, and A.M.Stock (2010).
Molecular strategies for phosphorylation-mediated regulation of response regulator activity.
  Curr Opin Microbiol, 13, 160-167.  
19244251 G.Minasov, S.Padavattan, L.Shuvalova, J.S.Brunzelle, D.J.Miller, A.Baslé, C.Massa, F.R.Collart, T.Schirmer, and W.F.Anderson (2009).
Crystal Structures of YkuI and Its Complex with Second Messenger Cyclic Di-GMP Suggest Catalytic Mechanism of Phosphodiester Bond Cleavage by EAL Domains.
  J Biol Chem, 284, 13174-13184.
PDB codes: 2bas 2w27
19898477 K.D.Smith, S.V.Lipchock, T.D.Ames, J.Wang, R.R.Breaker, and S.A.Strobel (2009).
Structural basis of ligand binding by a c-di-GMP riboswitch.
  Nat Struct Mol Biol, 16, 1218-1223.
PDB code: 3irw
19327118 K.Jonas, O.Melefors, and U.Römling (2009).
Regulation of c-di-GMP metabolism in biofilms.
  Future Microbiol, 4, 341-358.  
19679088 M.V.Navarro, N.De, N.Bae, Q.Wang, and H.Sondermann (2009).
Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX.
  Structure, 17, 1104-1116.  
19695263 N.De, M.V.Navarro, R.V.Raghavan, and H.Sondermann (2009).
Determinants for the activation and autoinhibition of the diguanylate cyclase response regulator WspR.
  J Mol Biol, 393, 619-633.
PDB codes: 3i5a 3i5b 3i5c
19287449 R.Hengge (2009).
Principles of c-di-GMP signalling in bacteria.
  Nat Rev Microbiol, 7, 263-273.  
19756011 T.Schirmer, and U.Jenal (2009).
Structural and mechanistic determinants of c-di-GMP signalling.
  Nat Rev Microbiol, 7, 724-735.  
18485075 J.W.Hickman, and C.S.Harwood (2008).
Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor.
  Mol Microbiol, 69, 376-389.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.