PDBsum entry 2c2a

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Transferase PDB id
Protein chain
241 a.a. *
Waters ×179
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of the entire cytoplasmic portion of a sensor histidine kinase protein
Structure: Sensor histidine kinase. Chain: a. Fragment: cytoplasmic portion residues 233-489. Synonym: histidine kinase tm0853. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
1.90Å     R-factor:   0.246     R-free:   0.275
Authors: A.Marina,C.D.Waldburger,W.A.Hendrickson
Key ref:
A.Marina et al. (2005). Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein. EMBO J, 24, 4247-4259. PubMed id: 16319927 DOI: 10.1038/sj.emboj.7600886
27-Sep-05     Release date:   21-Nov-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9WZV7  (Q9WZV7_THEMA) -  ATPase
489 a.a.
241 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     signal transduction   2 terms 
  Biochemical function     signal transducer activity     4 terms  


DOI no: 10.1038/sj.emboj.7600886 EMBO J 24:4247-4259 (2005)
PubMed id: 16319927  
Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein.
A.Marina, C.D.Waldburger, W.A.Hendrickson.
The large majority of histidine kinases (HKs) are multifunctional enzymes having autokinase, phosphotransfer and phosphatase activities, and most of these are transmembrane sensor proteins. Sensor HKs possess conserved cytoplasmic phosphorylation and ATP-binding kinase domains. The different enzymatic activities require participation by one or both of these domains, implying the need for different conformational states. The catalytic domains are linked to the membrane through a coiled-coil segment that sometimes includes other domains. We describe here the first crystal structure of the complete cytoplasmic region of a sensor HK, one from the thermophile Thermotoga maritima in complex with ADPbetaN at 1.9 A resolution. The structure reveals previously unidentified functions for several conserved residues and reveals the relative disposition of domains in a state seemingly poised for phosphotransfer. The structure thereby inspires hypotheses for the mechanisms of autophosphorylation, phosphotransfer and response-regulator dephosphorylation, and for signal transduction through the coiled-coil segment. Mutational tests support the functional relevance of interdomain contacts.
  Selected figure(s)  
Figure 6.
Figure 6 Interactions between DHp and CA domains. Stereoview of the structural elements involved in interdomain contacts and sulfate ion interactions. The DHp domain, CA domain and interdomain-connecting loop are represented in blue, gold and green ribbon diagrams, respectively. Additionally, the 1' helix, which presents His260' as a sulfate ligand, is shown in gray. The interacting side chains are shown as sticks with the same carbon atom color as the corresponding domain, except the sulfate-interacting residues that are in gray. Nitrogen, oxygen, sulfur and nucleotide molecule are drawn in blue, red, black and magenta, respectively. Residue labels take the colors of their domains. Hydrogen bonds and salt bridges between the sulfate ion and interacting residues are indicated by purple dots.
Figure 8.
Figure 8 Structure-based schematic of the reactions catalyzed by HK sensors. The kinase autophosphorylation (A arrow B), phosphotransferase (B arrow A^*) and phosphatase (A^* arrow A) activities are shown on projected outlines of the enzyme and protein-substrate models. Positions of N and C termini, ATP and the phospho-accepting histidine (H) are indicated on an HK dimer (orange and green). Position of phospho-accepting aspartate (D) is indicated on a RR (red). The transferred phosphoryl group is indicated as a yellow asterisk.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 4247-4259) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21347487 J.Perry, K.Koteva, and G.Wright (2011).
Receptor domains of two-component signal transduction systems.
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21250783 M.E.Auldridge, and K.T.Forest (2011).
Bacterial phytochromes: More than meets the light.
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20835487 A.Möglich, and K.Moffat (2010).
Engineered photoreceptors as novel optogenetic tools.
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21179024 A.Siryaporn, B.S.Perchuk, M.T.Laub, and M.Goulian (2010).
Evolving a robust signal transduction pathway from weak cross-talk.
  Mol Syst Biol, 6, 452.  
20534495 H.Li, J.Zhang, R.D.Vierstra, and H.Li (2010).
Quaternary organization of a phytochrome dimer as revealed by cryoelectron microscopy.
  Proc Natl Acad Sci U S A, 107, 10872-10877.  
20133181 H.Szurmant, and J.A.Hoch (2010).
Interaction fidelity in two-component signaling.
  Curr Opin Microbiol, 13, 190-197.  
20223701 J.Cheung, and W.A.Hendrickson (2010).
Sensor domains of two-component regulatory systems.
  Curr Opin Microbiol, 13, 116-123.  
20946854 J.S.Fassler, and A.H.West (2010).
Genetic and biochemical analysis of the SLN1 pathway in Saccharomyces cerevisiae.
  Methods Enzymol, 471, 291-317.  
20223700 L.J.Kenney (2010).
How important is the phosphatase activity of sensor kinases?
  Curr Opin Microbiol, 13, 168-176.  
20860483 P.D.Scheu, O.B.Kim, C.Griesinger, and G.Unden (2010).
Sensing by the membrane-bound sensor kinase DcuS: exogenous versus endogenous sensing of C(4)-dicarboxylates in bacteria.
  Future Microbiol, 5, 1383-1402.  
20453099 P.D.Scheu, Y.F.Liao, J.Bauer, H.Kneuper, T.Basché, G.Unden, and W.Erker (2010).
Oligomeric sensor kinase DcuS in the membrane of Escherichia coli and in proteoliposomes: chemical cross-linking and FRET spectroscopy.
  J Bacteriol, 192, 3474-3483.  
19906177 P.Slavny, R.Little, P.Salinas, T.A.Clarke, and R.Dixon (2010).
Quaternary structure changes in a second Per-Arnt-Sim domain mediate intramolecular redox signal relay in the NifL regulatory protein.
  Mol Microbiol, 75, 61-75.  
20404199 S.D.Goldberg, G.D.Clinthorne, M.Goulian, and W.F.DeGrado (2010).
Transmembrane polar interactions are required for signaling in the Escherichia coli sensor kinase PhoQ.
  Proc Natl Acad Sci U S A, 107, 8141-8146.  
20195256 S.I.O'Donoghue, D.S.Goodsell, A.S.Frangakis, F.Jossinet, R.A.Laskowski, M.Nilges, H.R.Saibil, A.Schafferhans, R.C.Wade, E.Westhof, and A.J.Olson (2010).
Visualization of macromolecular structures.
  Nat Methods, 7, S42-S55.  
20825354 T.Krell, J.Lacal, A.Busch, H.Silva-Jiménez, M.E.Guazzaroni, and J.L.Ramos (2010).
Bacterial sensor kinases: diversity in the recognition of environmental signals.
  Annu Rev Microbiol, 64, 539-559.  
19966007 V.Stewart, and L.L.Chen (2010).
The S helix mediates signal transmission as a HAMP domain coiled-coil extension in the NarX nitrate sensor from Escherichia coli K-12.
  J Bacteriol, 192, 734-745.  
20966074 Z.H.Chen, C.Schilde, and P.Schaap (2010).
Functional dissection of adenylate cyclase R, an inducer of spore encapsulation.
  J Biol Chem, 285, 41724-41731.  
19836329 A.Möglich, R.A.Ayers, and K.Moffat (2009).
Structure and signaling mechanism of Per-ARNT-Sim domains.
  Structure, 17, 1282-1294.  
20018738 A.Schug, M.Weigt, J.N.Onuchic, T.Hwa, and H.Szurmant (2009).
High-resolution protein complexes from integrating genomic information with molecular simulation.
  Proc Natl Acad Sci U S A, 106, 22124-22129.  
19805278 D.Albanesi, M.Martín, F.Trajtenberg, M.C.Mansilla, A.Haouz, P.M.Alzari, Mendoza, and A.Buschiazzo (2009).
Structural plasticity and catalysis regulation of a thermosensor histidine kinase.
  Proc Natl Acad Sci U S A, 106, 16185-16190.
PDB codes: 3ehf 3ehh 3ehj 3gie 3gif 3gig
19147840 E.Geisinger, T.W.Muir, and R.P.Novick (2009).
agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides.
  Proc Natl Acad Sci U S A, 106, 1216-1221.  
18931112 F.Scaramozzino, A.White, M.Perego, and J.A.Hoch (2009).
A unique GTP-dependent sporulation sensor histidine kinase in Bacillus anthracis.
  J Bacteriol, 191, 687-692.  
  19342776 H.Zhao, and L.Tang (2009).
Crystallographic characterization of a multidomain histidine protein kinase from an essential two-component regulatory system.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 346-349.  
19748334 J.J.Falke, and A.H.Erbse (2009).
The piston rises again.
  Structure, 17, 1149-1151.  
18922794 K.Emami, E.Topakas, T.Nagy, J.Henshaw, K.A.Jackson, K.E.Nelson, E.F.Mongodin, J.W.Murray, R.J.Lewis, and H.J.Gilbert (2009).
Regulation of the Xylan-degrading Apparatus of Cellvibrio japonicus by a Novel Two-component System.
  J Biol Chem, 284, 1086-1096.
PDB code: 2va0
19202292 K.Yamamoto, F.Matsumoto, S.Minagawa, T.Oshima, N.Fujita, N.Ogasawara, and A.Ishihama (2009).
Characterization of CitA-CitB signal transduction activating genes involved in anaerobic citrate catabolism in Escherichia coli.
  Biosci Biotechnol Biochem, 73, 346-350.  
19101565 M.J.Bick, V.Lamour, K.R.Rajashankar, Y.Gordiyenko, C.V.Robinson, and S.A.Darst (2009).
How to switch off a histidine kinase: crystal structure of Geobacillus stearothermophilus KinB with the inhibitor Sda.
  J Mol Biol, 386, 163-177.
PDB code: 3d36
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.  
19558698 N.Li, F.Wang, S.Niu, J.Cao, K.Wu, Y.Li, N.Yin, X.Zhang, W.Zhu, and Y.Yin (2009).
Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK).
  BMC Microbiol, 9, 129.  
19800110 P.Casino, V.Rubio, and A.Marina (2009).
Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction.
  Cell, 139, 325-336.
PDB codes: 3dge 3dgf 3gl9
19575571 R.Gao, and A.M.Stock (2009).
Biological insights from structures of two-component proteins.
  Annu Rev Microbiol, 63, 133-154.  
19836334 S.Yamada, H.Sugimoto, M.Kobayashi, A.Ohno, H.Nakamura, and Y.Shiro (2009).
Structure of PAS-linked histidine kinase and the response regulator complex.
  Structure, 17, 1333-1344.
PDB codes: 3a0r 3a0s 3a0t 3a0u 3a0v 3a0w 3a0x 3a0y 3a0z 3a10
19783630 Y.E.Chen, C.G.Tsokos, E.G.Biondi, B.S.Perchuk, and M.T.Laub (2009).
Dynamics of two Phosphorelays controlling cell cycle progression in Caulobacter crescentus.
  J Bacteriol, 191, 7417-7429.  
18214466 C.Neylon (2008).
Small angle neutron and X-ray scattering in structural biology: recent examples from the literature.
  Eur Biophys J, 37, 531-541.  
18588317 H.Szurmant, B.G.Bobay, R.A.White, D.M.Sullivan, R.J.Thompson, T.Hwa, J.A.Hoch, and J.Cavanagh (2008).
Co-evolving motions at protein-protein interfaces of two-component signaling systems identified by covariance analysis.
  Biochemistry, 47, 7782-7784.  
18555780 J.M.Skerker, B.S.Perchuk, A.Siryaporn, E.A.Lubin, O.Ashenberg, M.Goulian, and M.T.Laub (2008).
Rewiring the specificity of two-component signal transduction systems.
  Cell, 133, 1043-1054.  
18820688 M.Etzkorn, H.Kneuper, P.Dünnwald, V.Vijayan, J.Krämer, C.Griesinger, S.Becker, G.Unden, and M.Baldus (2008).
Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS.
  Nat Struct Mol Biol, 15, 1031-1039.
PDB code: 2w0n
18771590 R.A.Sharrock (2008).
The phytochrome red/far-red photoreceptor superfamily.
  Genome Biol, 9, 230.  
18799746 X.Yang, J.Kuk, and K.Moffat (2008).
Crystal structure of Pseudomonas aeruginosa bacteriophytochrome: photoconversion and signal transduction.
  Proc Natl Acad Sci U S A, 105, 14715-14720.
PDB code: 3c2w
17085571 A.Eldakak, and F.M.Hulett (2007).
Cys303 in the histidine kinase PhoR is crucial for the phosphotransfer reaction in the PhoPR two-component system in Bacillus subtilis.
  J Bacteriol, 189, 410-421.  
17913492 H.Szurmant, R.A.White, and J.A.Hoch (2007).
Sensor complexes regulating two-component signal transduction.
  Curr Opin Struct Biol, 17, 706-715.  
18076326 M.T.Laub, and M.Goulian (2007).
Specificity in two-component signal transduction pathways.
  Annu Rev Genet, 41, 121-145.  
17573470 R.Gao, and D.G.Lynn (2007).
Integration of rotation and piston motions in coiled-coil signal transduction.
  J Bacteriol, 189, 6048-6056.  
17355964 R.Little, I.Martinez-Argudo, S.Perry, and R.Dixon (2007).
Role of the H domain of the histidine kinase-like protein NifL in signal transmission.
  J Biol Chem, 282, 13429-13437.  
17827294 S.J.Reisinger, S.Huntwork, P.H.Viollier, and K.R.Ryan (2007).
DivL performs critical cell cycle functions in Caulobacter crescentus independent of kinase activity.
  J Bacteriol, 189, 8308-8320.  
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
17021619 A.M.Stock (2006).
Transmembrane signaling by asymmetry.
  Nat Struct Mol Biol, 13, 862-863.  
16965536 H.Dortay, N.Mehnert, L.Bürkle, T.Schmülling, and A.Heyl (2006).
Analysis of protein interactions within the cytokinin-signaling pathway of Arabidopsis thaliana.
  FEBS J, 273, 4631-4644.  
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
16990134 M.B.Neiditch, M.J.Federle, A.J.Pompeani, R.C.Kelly, D.L.Swem, P.D.Jeffrey, B.L.Bassler, and F.M.Hughson (2006).
Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing.
  Cell, 126, 1095-1108.
PDB codes: 2hj9 2hje
17158704 T.Mascher, J.D.Helmann, and G.Unden (2006).
Stimulus perception in bacterial signal-transducing histidine kinases.
  Microbiol Mol Biol Rev, 70, 910-938.  
16953892 V.Anantharaman, S.Balaji, and L.Aravind (2006).
The signaling helix: a common functional theme in diverse signaling proteins.
  Biol Direct, 1, 25.  
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.