PDBsum entry 1xhe

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protein Protein-protein interface(s) links
Transcription PDB id
Protein chains
121 a.a. *
Waters ×69
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of the receiver domain of redox response regulator arca
Structure: Aerobic respiration control protein arca. Chain: a, b. Fragment: receiver domain. Synonym: redox response regulator arca. Dye resistance protein. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: arca, dye, fexa, sfra, seg, msp, cpxc. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.50Å     R-factor:   0.215     R-free:   0.256
Authors: A.Toro-Roman,T.R.Mack,A.M.Stock
Key ref:
A.Toro-Roman et al. (2005). Structural analysis and solution studies of the activated regulatory domain of the response regulator ArcA: a symmetric dimer mediated by the alpha4-beta5-alpha5 face. J Mol Biol, 349, 11-26. PubMed id: 15876365 DOI: 10.1016/j.jmb.2005.03.059
18-Sep-04     Release date:   17-May-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A9Q1  (ARCA_ECOLI) -  Aerobic respiration control protein ArcA
238 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     two-component signal transduction system (phosphorelay)   1 term 
  Biochemical function     two-component response regulator activity     1 term  


DOI no: 10.1016/j.jmb.2005.03.059 J Mol Biol 349:11-26 (2005)
PubMed id: 15876365  
Structural analysis and solution studies of the activated regulatory domain of the response regulator ArcA: a symmetric dimer mediated by the alpha4-beta5-alpha5 face.
A.Toro-Roman, T.R.Mack, A.M.Stock.
Escherichia coli react to changes from aerobic to anaerobic conditions of growth using the ArcA-ArcB two-component signal transduction system. This system, in conjunction with other proteins, regulates the respiratory metabolic pathways in the organism. ArcA is a member of the OmpR/PhoB subfamily of response regulator transcription factors that are known to regulate transcription by binding in tandem to target DNA direct repeats. It is still unclear in this subfamily how activation by phosphorylation of the regulatory domain of response regulators stimulates DNA binding by the effector domain and how dimerization and domain orientation, as well as intra- and intermolecular interactions, affect this process. In order to address these questions we have solved the crystal structures of the regulatory domain of ArcA in the presence and absence of the phosphoryl analog, BeF3-. In the crystal structures, the regulatory domain of ArcA forms a symmetric dimer mediated by the alpha4-beta5-alpha5 face of the protein and involving a number of residues that are highly conserved in the OmpR/PhoB subfamily. It is hypothesized that members of this subfamily use a common mechanism of regulation by dimerization. Additional biophysical studies were employed to probe the oligomerization state of ArcA, as well as its individual domains, in solution. The solution studies show the propensity of the individual domains to associate into oligomers larger than the dimer observed for the intact protein, and suggest that the C-terminal DNA-binding domain also plays a role in oligomerization.
  Selected figure(s)  
Figure 1.
Figure 1. Ribbon diagram and surface representation of the Click to view the MathML source- [0?wchp=dGLbVtz-zSkWA] -activated regulatory domain of ArcA. The protomers that make up the dimer are shown in gold and teal. The 2-fold rotationally symmetric dimer is mediated by the a4-b5-a5 face, which buries 1700 Å2 of surface area at the interface (850 Å2 per monomer). Side-chains of Asp54, Thr81 and Tyr100 (gray and red), Click to view the MathML source- [0?wchp=dGLbVtz-zSkWA] (magenta) and the catalytic Mg2+ (green) are shown as ball-and-stick models. Figures were created using Pymol (
Figure 4.
Figure 4. Intermolecular interactions at the a4-b5-a5 dimer interface. (a) The core of a hydrophobic patch (spheres) that brings helices a4 and a5 together is formed between Ile90 (a4), Leu93 (a4) and Ile112 (a5). (b) The interface is further stabilized by an extensive network of salt bridges (ball-and-stick models, yellow dotted lines) formed between Lys89 (a4)-Glu109 (a5), Asp99 (b5)-Arg113 (a5), Glu94 (a4)-Arg115 (a5) and Asp98 (a4-b5 loop)-Arg120 (a5). Protomers are distinguished by colors gold and teal.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 349, 11-26) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20111065 Y.Gotoh, A.Doi, E.Furuta, S.Dubrac, Y.Ishizaki, M.Okada, M.Igarashi, N.Misawa, H.Yoshikawa, T.Okajima, T.Msadek, and R.Utsumi (2010).
Novel antibacterial compounds specifically targeting the essential WalR response regulator.
  J Antibiot (Tokyo), 63, 127-134.  
19223448 C.Yanover, M.Singh, and E.Zaslavsky (2009).
M are better than one: an ensemble-based motif finder and its application to regulatory element prediction.
  Bioinformatics, 25, 868-874.  
19116270 M.Weigt, R.A.White, H.Szurmant, J.A.Hoch, and T.Hwa (2009).
Identification of direct residue contacts in protein-protein interaction by message passing.
  Proc Natl Acad Sci U S A, 106, 67-72.  
19575571 R.Gao, and A.M.Stock (2009).
Biological insights from structures of two-component proteins.
  Annu Rev Microbiol, 63, 133-154.  
19820095 S.Gupta, A.Pathak, A.Sinha, and D.Sarkar (2009).
Mycobacterium tuberculosis PhoP recognizes two adjacent direct-repeat sequences to form head-to-head dimers.
  J Bacteriol, 191, 7466-7476.  
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.  
19246239 U.Jenal, and M.Y.Galperin (2009).
Single domain response regulators: molecular switches with emerging roles in cell organization and dynamics.
  Curr Opin Microbiol, 12, 152-160.  
19542275 W.Spencer, R.Siam, M.C.Ouimet, D.P.Bastedo, and G.T.Marczynski (2009).
CtrA, a global response regulator, uses a distinct second category of weak DNA binding sites for cell cycle transcription control in Caulobacter crescentus.
  J Bacteriol, 191, 5458-5470.  
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.  
18832306 D.Ruiz, P.Salinas, M.L.Lopez-Redondo, M.L.Cayuela, A.Marina, and A.Contreras (2008).
Phosphorylation-independent activation of the atypical response regulator NblR.
  Microbiology, 154, 3002-3015.  
18353359 G.Wisedchaisri, M.Wu, D.R.Sherman, and W.G.Hol (2008).
Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation.
  J Mol Biol, 378, 227-242.
PDB codes: 3c3w 3c57
18195018 J.E.Rhee, W.Sheng, L.K.Morgan, R.Nolet, X.Liao, and L.J.Kenney (2008).
Amino acids important for DNA recognition by the response regulator OmpR.
  J Biol Chem, 283, 8664-8677.  
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.  
18557815 S.A.Thomas, J.A.Brewster, and R.B.Bourret (2008).
Two variable active site residues modulate response regulator phosphoryl group stability.
  Mol Microbiol, 69, 453-465.  
18653527 X.Wang, H.Gao, Y.Shen, G.M.Weinstock, J.Zhou, and T.Palzkill (2008).
A high-throughput percentage-of-binding strategy to measure binding energies in DNA-protein interactions: application to genome-scale site discovery.
  Nucleic Acids Res, 36, 4863-4871.  
18076904 X.Zhao, D.M.Copeland, A.S.Soares, and A.H.West (2008).
Crystal structure of a complex between the phosphorelay protein YPD1 and the response regulator domain of SLN1 bound to a phosphoryl analog.
  J Mol Biol, 375, 1141-1151.
PDB code: 2r25
17313674 D.A.Ravcheev, A.V.Gerasimova, A.A.Mironov, and M.S.Gelfand (2007).
Comparative genomic analysis of regulation of anaerobic respiration in ten genomes from three families of gamma-proteobacteria (Enterobacteriaceae, Pasteurellaceae, Vibrionaceae).
  BMC Genomics, 8, 54.  
17491010 E.Hong, H.M.Lee, H.Ko, D.U.Kim, B.Y.Jeon, J.Jung, J.Shin, S.A.Lee, Y.Kim, Y.H.Jeon, C.Cheong, H.S.Cho, and W.Lee (2007).
Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism.
  J Biol Chem, 282, 20667-20675.
PDB codes: 2hqn 2hqo 2hqr
17511470 N.Friedland, T.R.Mack, M.Yu, L.W.Hung, T.C.Terwilliger, G.S.Waldo, and A.M.Stock (2007).
Domain orientation in the inactive response regulator Mycobacterium tuberculosis MtrA provides a barrier to activation.
  Biochemistry, 46, 6733-6743.
PDB code: 2gwr
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
17697997 P.Wassmann, C.Chan, R.Paul, A.Beck, H.Heerklotz, U.Jenal, and T.Schirmer (2007).
Structure of BeF3- -modified response regulator PleD: implications for diguanylate cyclase activation, catalysis, and feedback inhibition.
  Structure, 15, 915-927.
PDB code: 2v0n
17182055 R.Arribas-Bosacoma, S.K.Kim, C.Ferrer-Orta, A.G.Blanco, P.J.Pereira, F.X.Gomis-Rüth, B.L.Wanner, M.Coll, and M.Solà (2007).
The X-ray crystal structures of two constitutively active mutants of the Escherichia coli PhoB receiver domain give insights into activation.
  J Mol Biol, 366, 626-641.
PDB codes: 2jb9 2jba
17433693 R.Gao, T.R.Mack, and A.M.Stock (2007).
Bacterial response regulators: versatile regulatory strategies from common domains.
  Trends Biochem Sci, 32, 225-234.  
17640875 R.Paul, S.Abel, P.Wassmann, A.Beck, H.Heerklotz, and U.Jenal (2007).
Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization.
  J Biol Chem, 282, 29170-29177.  
18052041 S.Wang, J.Engohang-Ndong, and I.Smith (2007).
Structure of the DNA-binding domain of the response regulator PhoP from Mycobacterium tuberculosis.
  Biochemistry, 46, 14751-14761.
PDB code: 2pmu
17322531 T.Gao, X.Zhang, N.B.Ivleva, S.S.Golden, and A.LiWang (2007).
NMR structure of the pseudo-receiver domain of CikA.
  Protein Sci, 16, 465-475.
PDB code: 2j48
16788170 A.A.Gusa, J.Gao, V.Stringer, G.Churchward, and J.R.Scott (2006).
Phosphorylation of the group A Streptococcal CovR response regulator causes dimerization and promoter-specific recruitment by RNA polymerase.
  J Bacteriol, 188, 4620-4626.  
16784239 C.Laguri, R.A.Stenzel, T.J.Donohue, M.K.Phillips-Jones, and M.P.Williamson (2006).
Activation of the global gene regulator PrrA (RegA) from Rhodobacter sphaeroides.
  Biochemistry, 45, 7872-7881.  
16788205 K.I.Varughese, I.Tsigelny, and H.Zhao (2006).
The crystal structure of beryllofluoride Spo0F in complex with the phosphotransferase Spo0B represents a phosphotransfer pretransition state.
  J Bacteriol, 188, 4970-4977.
PDB code: 2ftk
16771670 R.Malpica, G.R.Sandoval, C.Rodríguez, B.Franco, and D.Georgellis (2006).
Signaling by the arc two-component system provides a link between the redox state of the quinone pool and gene expression.
  Antioxid Redox Signal, 8, 781-795.  
16618701 T.Yoshida, L.Qin, L.A.Egger, and M.Inouye (2006).
Transcription regulation of ompF and ompC by a single transcription factor, OmpR.
  J Biol Chem, 281, 17114-17123.  
16322582 A.Toro-Roman, T.Wu, and A.M.Stock (2005).
A common dimerization interface in bacterial response regulators KdpE and TorR.
  Protein Sci, 14, 3077-3088.
PDB codes: 1zgz 1zh2 1zh4
16154092 P.Bachhawat, G.V.Swapna, G.T.Montelione, and A.M.Stock (2005).
Mechanism of activation for transcription factor PhoB suggested by different modes of dimerization in the inactive and active states.
  Structure, 13, 1353-1363.
PDB code: 1zes
16154079 W.R.McCleary (2005).
No phobias about PhoB activation.
  Structure, 13, 1238-1239.  
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.