PDBsum entry 2gwr

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Signaling protein PDB id
Protein chain
225 a.a. *
GOL ×2
Waters ×80
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Crystal structure of the response regulator protein mtra fro mycobacterium tuberculosis
Structure: DNA-binding response regulator mtra. Chain: a. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: mt3344, mtcy20b11.21c, mtra, rv3246c. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.204     R-free:   0.244
Authors: N.Friedland,T.R.Mack,M.Yu,E.H.Bursey,L.W.Hung,A.M.Stock,G.S. T.C.Terwilliger
Key ref: N.Friedland et al. (2007). Domain orientation in the inactive response regulator Mycobacterium tuberculosis MtrA provides a barrier to activation. Biochemistry, 46, 6733-6743. PubMed id: 17511470
05-May-06     Release date:   23-May-06    
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Protein chain
P9WGM7  (MTRA_MYCTU) -  DNA-binding response regulator MtrA
228 a.a.
225 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   2 terms 
  Biological process     intracellular signal transduction   4 terms 
  Biochemical function     two-component response regulator activity     3 terms  


Biochemistry 46:6733-6743 (2007)
PubMed id: 17511470  
Domain orientation in the inactive response regulator Mycobacterium tuberculosis MtrA provides a barrier to activation.
N.Friedland, T.R.Mack, M.Yu, L.W.Hung, T.C.Terwilliger, G.S.Waldo, A.M.Stock.
The structure of MtrA, an essential gene product for the human pathogen Mycobacterium tuberculosis, has been solved to a resolution of 2.1 A. MtrA is a member of the OmpR/PhoB family of response regulators and represents the fourth family member for which a structure of the protein in its inactive state has been determined. As is true for all OmpR/PhoB family members, MtrA possesses an N-terminal regulatory domain and a C-terminal winged helix-turn-helix DNA-binding domain, with phosphorylation of the regulatory domain modulating the activity of the protein. In the inactive form of MtrA, these two domains form an extensive interface that is composed of the alpha4-beta5-alpha5 face of the regulatory domain and the C-terminal end of the positioning helix, the trans-activation loop, and the recognition helix of the DNA-binding domain. This domain orientation suggests a mechanism of mutual inhibition by the two domains. Activation of MtrA would require a disruption of this interface to allow the alpha4-beta5-alpha5 face of the regulatory domain to form the intermolecule interactions that are associated with the active state and to allow the recognition helix to interact with DNA. Furthermore, the interface appears to stabilize the inactive conformation of MtrA, potentially reducing the rate of phosphorylation of the N-terminal domain. This combination of effects may form a switch, regulating the activity of MtrA. The domain orientation exhibited by MtrA also provides a rationale for the variation in linker length that is observed within the OmpR/PhoB family of response regulators.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21295603 M.Al Zayer, D.Stankowska, R.Dziedzic, K.Sarva, M.V.Madiraju, and M.Rajagopalan (2011).
MycobacteriumtuberculosismtrA merodiploid strains with point mutations in the signal-receiving domain of MtrA exhibit growth defects in nutrient broth.
  Plasmid, 65, 210-218.  
20702407 C.M.Barbieri, T.R.Mack, V.L.Robinson, M.T.Miller, and A.M.Stock (2010).
Regulation of response regulator autophosphorylation through interdomain contacts.
  J Biol Chem, 285, 32325-32335.
PDB codes: 3nhz 3nnn 3nns
20080056 R.Gao, and A.M.Stock (2010).
Molecular strategies for phosphorylation-mediated regulation of response regulator activity.
  Curr Opin Microbiol, 13, 160-167.  
20671191 Y.Li, J.Zeng, and Z.G.He (2010).
Characterization of a functional C-terminus of the Mycobacterium tuberculosis MtrA responsible for both DNA binding and interaction with its two-component partner protein, MtrB.
  J Biochem, 148, 549-556.  
19575571 R.Gao, and A.M.Stock (2009).
Biological insights from structures of two-component proteins.
  Annu Rev Microbiol, 63, 133-154.  
19371748 T.R.Mack, R.Gao, and A.M.Stock (2009).
Probing the roles of the two different dimers mediated by the receiver domain of the response regulator PhoB.
  J Mol Biol, 389, 349-364.  
18328252 C.M.Barbieri, and A.M.Stock (2008).
Universally applicable methods for monitoring response regulator aspartate phosphorylation both in vitro and in vivo using Phos-tag-based reagents.
  Anal Biochem, 376, 73-82.  
18631241 R.Gao, Y.Tao, and A.M.Stock (2008).
System-level mapping of Escherichia coli response regulator dimerization with FRET hybrids.
  Mol Microbiol, 69, 1358-1372.  
17942407 J.King-Scott, E.Nowak, E.Mylonas, S.Panjikar, M.Roessle, D.I.Svergun, and P.A.Tucker (2007).
The structure of a full-length response regulator from Mycobacterium tuberculosis in a stabilized three-dimensional domain-swapped, activated state.
  J Biol Chem, 282, 37717-37729.
PDB code: 2oqr
17545283 P.Bachhawat, and A.M.Stock (2007).
Crystal structures of the receiver domain of the response regulator PhoP from Escherichia coli in the absence and presence of the phosphoryl analog beryllofluoride.
  J Bacteriol, 189, 5987-5995.
PDB codes: 2pkx 2pl1
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.