Abstract
Chemoreceptor arrays are supramolecular transmembrane machines of unknown structure that allow bacteria to sense their surroundings and respond by chemotaxis. We have combined X-ray crystallography of purified proteins with electron cryotomography of native arrays inside cells to reveal the arrangement of the component transmembrane receptors, histidine kinases (CheA) and CheW coupling proteins. Trimers of receptor dimers lie at the vertices of a hexagonal lattice in a “two-facing-two” configuration surrounding a ring of alternating CheA regulatory domains (P5) and CheW couplers. Whereas the CheA kinase domains (P4) project downward below the ring, the CheA dimerization domains (P3) link neighboring rings to form an extended, stable array. This highly interconnected protein architecture underlies the remarkable sensitivity and cooperative nature of transmembrane signaling in bacterial chemotaxis.
Bibliography
Briegel, A., Li, X., Bilwes, A. M., Hughes, K. T., Jensen, G. J., & Crane, B. R. (2012). Bacterial chemoreceptor arrays are hexagonally packed trimers of receptor dimers networked by rings of kinase and coupling proteins. Proceedings of the National Academy of Sciences, 109(10), 3766â3771.
References
62
Referenced
249
-
GL Hazelbauer, JJ Falke, JS Parkinson, Bacterial chemoreceptors: High-performance signaling in networked arrays. Trends Biochem Sci 33, 9–19 (2008).
(
10.1016/j.tibs.2007.09.014
) / Trends Biochem Sci / Bacterial chemoreceptors: High-performance signaling in networked arrays by Hazelbauer GL (2008) -
D Kentner, V Sourjik, Spatial organization of the bacterial chemotaxis system. Curr Opin Microbiol 9, 619–624 (2006).
(
10.1016/j.mib.2006.10.012
) / Curr Opin Microbiol / Spatial organization of the bacterial chemotaxis system by Kentner D (2006) -
GH Wadhams, JP Armitage, Making sense of it all: Bacterial chemotaxis. Nat Rev Mol Cell Biol 5, 1024–1037 (2004).
(
10.1038/nrm1524
) / Nat Rev Mol Cell Biol / Making sense of it all: Bacterial chemotaxis by Wadhams GH (2004) -
D Greenfield, et al., Self-organization of the Escherichia coli chemotaxis network imaged with super resolution light microscopy. PLoS Biol 7, e1000137 (2009).
(
10.1371/journal.pbio.1000137
) / PLoS Biol / Self-organization of the Escherichia coli chemotaxis network imaged with super resolution light microscopy by Greenfield D (2009) -
V Sourjik, HC Berg, Localization of components of the chemotaxis machinery of Escherichia coli using fluorescent protein fusions. Mol Microbiol 37, 740–751 (2000).
(
10.1046/j.1365-2958.2000.02044.x
) / Mol Microbiol / Localization of components of the chemotaxis machinery of Escherichia coli using fluorescent protein fusions by Sourjik V (2000) -
DL Englert, CA Adase, A Jayaraman, MD Manson, Repellent taxis in response to nickel ion reqires neither Ni2+ transport nor the periplasmic NikA binding protein. J Bacteriol 192, 2633–2637 (2010).
(
10.1128/JB.00854-09
) / J Bacteriol / Repellent taxis in response to nickel ion reqires neither Ni2+ transport nor the periplasmic NikA binding protein by Englert DL (2010) -
MV Milburn, et al., Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science 254, 1342–1347 (1991).
(
10.1126/science.1660187
) / Science / Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand by Milburn MV (1991) -
R Tam, MHJ Saier, Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol Rev 57, 320–346 (1993).
(
10.1128/mr.57.2.320-346.1993
) / Microbiol Rev / Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria by Tam R (1993) -
A Briegel, et al., Universal architecture of bacterial chemoreceptor arrays. Proc Natl Acad Sci USA 106, 17181–17186 (2009).
(
10.1073/pnas.0905181106
) / Proc Natl Acad Sci USA / Universal architecture of bacterial chemoreceptor arrays by Briegel A (2009) -
AM Bilwes, LA Alex, BR Crane, MI Simon, Structure of CheA, a signal-transducing histidine kinase. Cell 96, 131–141 (1999).
(
10.1016/S0092-8674(00)80966-6
) / Cell / Structure of CheA, a signal-transducing histidine kinase by Bilwes AM (1999) - AM Bilwes, SY Park, CM Quezada, MI Simon, BR Crane Histidine Kinases in Signal Transduction, eds M Inouye, R Dutta (Academic, San Diego), pp. 48–74 (2003). / Histidine Kinases in Signal Transduction by Bilwes AM (2003)
-
S-Y Park, CM Quezada, AM Bilwes, BR Crane, Subunit exchange by CheA histidine kinases from the mesophile Escherichia coli and the thermophile Thermotoga maritima. Biochemistry 43, 2228–2240 (2004).
(
10.1021/bi0352419
) / Biochemistry / Subunit exchange by CheA histidine kinases from the mesophile Escherichia coli and the thermophile Thermotoga maritima by Park S-Y (2004) -
CM Quezada, G Gradinaru, MI Simon, AM Bilwes, BR Crane, Helical shifts generate two distinct conformers in the atomic resolution structure of the CheA phosphotransferase domain from Thermotoga maritima. J Mol Biol 341, 1283–1294 (2004).
(
10.1016/j.jmb.2004.06.061
) / J Mol Biol / Helical shifts generate two distinct conformers in the atomic resolution structure of the CheA phosphotransferase domain from Thermotoga maritima by Quezada CM (2004) -
L Turner, WS Ryu, HC Berg, Real-time imaging of fluorescent flagellar filaments. J Bacteriol 182, 2793–2801 (2000).
(
10.1128/JB.182.10.2793-2801.2000
) / J Bacteriol / Real-time imaging of fluorescent flagellar filaments by Turner L (2000) -
SJ Kleene, AC Hobson, J Adler, Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli. Proc Natl Acad Sci USA 76, 6309–6313 (1979).
(
10.1073/pnas.76.12.6309
) / Proc Natl Acad Sci USA / Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli by Kleene SJ (1979) -
A Lupas, J Stock, Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis. J Biol Chem 264, 17337–17342 (1989).
(
10.1016/S0021-9258(18)71497-X
) / J Biol Chem / Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis by Lupas A (1989) -
ML Toews, MF Goy, MS Springer, J Adler, Attractants and repellents control demethylation of methylated chemotaxis proteins in Escherichia coli. Proc Natl Acad Sci USA 76, 5544–5548 (1979).
(
10.1073/pnas.76.11.5544
) / Proc Natl Acad Sci USA / Attractants and repellents control demethylation of methylated chemotaxis proteins in Escherichia coli by Toews ML (1979) -
TAJ Duke, D Bray, Heightened sensitivity of a lattice of membrane receptors. Proc Natl Acad Sci USA 96, 10104–10108 (1999).
(
10.1073/pnas.96.18.10104
) / Proc Natl Acad Sci USA / Heightened sensitivity of a lattice of membrane receptors by Duke TAJ (1999) -
RG Endres, NS Wingreen, Precise adaptation in bacterial chemotaxis through “assistance neighborhoods”. Proc Natl Acad Sci USA 103, 13040–13044 (2006).
(
10.1073/pnas.0603101103
) / Proc Natl Acad Sci USA / Precise adaptation in bacterial chemotaxis through “assistance neighborhoods” by Endres RG (2006) -
JE Gestwicki, LL Kiessling, Inter-receptor communication through arrays of bacterial chemoreceptors. Nature 415, 81–84 (2002).
(
10.1038/415081a
) / Nature / Inter-receptor communication through arrays of bacterial chemoreceptors by Gestwicki JE (2002) -
G Li, RM Weis, Covalent modification regulates ligand binding to receptor complexes in the chemosensory system of Escherichia coli. Cell 100, 357–365 (2000).
(
10.1016/S0092-8674(00)80671-6
) / Cell / Covalent modification regulates ligand binding to receptor complexes in the chemosensory system of Escherichia coli by Li G (2000) -
M Li, GL Hazelbauer, Adaptational assistance in clusters of bacterial chemoreceptors. Mol Microbiol 56, 1617–1626 (2005).
(
10.1111/j.1365-2958.2005.04641.x
) / Mol Microbiol / Adaptational assistance in clusters of bacterial chemoreceptors by Li M (2005) -
V Sourjik, H Berg, Receptor sensitivity in bacterial chemotaxis. Proc Natl Acad Sci USA 99, 123–127 (2002).
(
10.1073/pnas.011589998
) / Proc Natl Acad Sci USA / Receptor sensitivity in bacterial chemotaxis by Sourjik V (2002) -
V Sourjik, HC Berg, Functional interactions between receptors in bacterial chemotaxis. Nature 428, 437–441 (2004).
(
10.1038/nature02406
) / Nature / Functional interactions between receptors in bacterial chemotaxis by Sourjik V (2004) -
A Briegel, et al., Location and architecture of the Caulobacter crescentus chemoreceptor array. Mol Microbiol 69, 30–41 (2008).
(
10.1111/j.1365-2958.2008.06219.x
) / Mol Microbiol / Location and architecture of the Caulobacter crescentus chemoreceptor array by Briegel A (2008) -
CM Khursigara, X Wu, S Subramaniam, Chemoreceptors in Caulobacter crescentus: Trimers of receptor dimers in a partially ordered hexagonally packed array. J Bacteriol 190, 6805–6810 (2008).
(
10.1128/JB.00640-08
) / J Bacteriol / Chemoreceptors in Caulobacter crescentus: Trimers of receptor dimers in a partially ordered hexagonally packed array by Khursigara CM (2008) -
KK Kim, H Yokota, SH Kim, Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor. Nature 400, 787–792 (1999).
(
10.1038/23512
) / Nature / Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor by Kim KK (1999) -
MD Coleman, RB Bass, RS Mehan, JJ Falke, Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switching. Biochemistry 44, 7687–7695 (2005).
(
10.1021/bi0501479
) / Biochemistry / Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switching by Coleman MD (2005) -
S-Y Park, et al., Reconstruction of the chemotaxis receptor-kinase assembly. Nat Struct Mol Biol 13, 400–407 (2006).
(
10.1038/nsmb1085
) / Nat Struct Mol Biol / Reconstruction of the chemotaxis receptor-kinase assembly by Park S-Y (2006) -
AM Pollard, AM Bilwes, BR Crane, The structure of a soluble chemoreceptor suggests a mechanism for propagating conformational signals. Biochemistry 48, 1936–1944 (2009).
(
10.1021/bi801727m
) / Biochemistry / The structure of a soluble chemoreceptor suggests a mechanism for propagating conformational signals by Pollard AM (2009) -
IJ Griswold, et al., The solution structure and interactions of CheW from Thermotoga maritima. Nat Struct Mol Biol 9, 121–125 (2002).
(
10.1038/nsb753
) / Nat Struct Mol Biol / The solution structure and interactions of CheW from Thermotoga maritima by Griswold IJ (2002) -
J Zhao, JS Parkinson, Mutational analysis of the chemoreceptor-coupling domain of the Escherichia coli chemotaxis signaling kinase CheA. J Bacteriol 188, 3299–3307 (2006).
(
10.1128/JB.188.9.3299-3307.2006
) / J Bacteriol / Mutational analysis of the chemoreceptor-coupling domain of the Escherichia coli chemotaxis signaling kinase CheA by Zhao J (2006) -
J Bhatnagar, et al., Structure of the ternary complex formed by a chemotaxis receptor signalling domain, the CheA histidine kinase, and the coupling protein CheW as determined by pulsed dipolar ESR spectroscopy. Biochemistry 49, 3824–3841 (2010).
(
10.1021/bi100055m
) / Biochemistry / Structure of the ternary complex formed by a chemotaxis receptor signalling domain, the CheA histidine kinase, and the coupling protein CheW as determined by pulsed dipolar ESR spectroscopy by Bhatnagar J (2010) -
M Boukhvalova, R VanBruggen, RC Stewart, CheA kinase and chemoreceptor interaction surfaces on CheW. J Biol Chem 277, 23596–23603 (2002).
(
10.1074/jbc.M202288200
) / J Biol Chem / CheA kinase and chemoreceptor interaction surfaces on CheW by Boukhvalova M (2002) -
ES Underbakke, YM Zhu, LL Kiessling, Protein footprinting in a complex milieu: Identifying the interaction surfaces of the chemotaxis adaptor protein CheW. J Mol Biol 409, 483–495 (2011).
(
10.1016/j.jmb.2011.03.040
) / J Mol Biol / Protein footprinting in a complex milieu: Identifying the interaction surfaces of the chemotaxis adaptor protein CheW by Underbakke ES (2011) -
CA Studdert, JS Parkinson, Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies. Proc Natl Acad Sci USA 102, 15623–15628 (2005).
(
10.1073/pnas.0506040102
) / Proc Natl Acad Sci USA / Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies by Studdert CA (2005) -
MN Levit, TW Grebe, JB Stock, Organization of the receptor-kinas signaling array that regulates the Escherichia coli chemotaxis. J Biol Chem 277, 36748–36754 (2002).
(
10.1074/jbc.M204317200
) / J Biol Chem / Organization of the receptor-kinas signaling array that regulates the Escherichia coli chemotaxis by Levit MN (2002) -
D Kentner, SMH Thiem, V Sourjik, Determinants of chemoreceptor cluster formation in Escherichia coli. Mol Microbiol 61, 407–417 (2006).
(
10.1111/j.1365-2958.2006.05250.x
) / Mol Microbiol / Determinants of chemoreceptor cluster formation in Escherichia coli by Kentner D (2006) -
AE Asinas, RM Weis, Competitive and cooperative interactions in receptor signaling complexes. J Biol Chem 281, 30512–30523 (2006).
(
10.1074/jbc.M606267200
) / J Biol Chem / Competitive and cooperative interactions in receptor signaling complexes by Asinas AE (2006) -
AS Miller, SC Kohout, KA Gilman, JJ Falke, CheA kinase of bacterial chemotaxis: Chemical mapping of four essential docking sites. Biochemistry 45, 8699–8711 (2006).
(
10.1021/bi060580y
) / Biochemistry / CheA kinase of bacterial chemotaxis: Chemical mapping of four essential docking sites by Miller AS (2006) -
M Li, GL Hazelbauer, Core unit of chemotaxis signaling complexes. Proc Natl Acad Sci USA 108, 9390–9395 (2011).
(
10.1073/pnas.1104824108
) / Proc Natl Acad Sci USA / Core unit of chemotaxis signaling complexes by Li M (2011) -
M Li, GL Hazelbauer, Cellular stoichiometry of the components of the chemotaxis signalling complex. J Bacteriol 186, 3687–3694 (2004).
(
10.1128/JB.186.12.3687-3694.2004
) / J Bacteriol / Cellular stoichiometry of the components of the chemotaxis signalling complex by Li M (2004) -
AH Erbse, JJ Falke, The core signaling proteins of bacterial chemotaxis assemble to form an ultrastable complex. Biochemistry 48, 6975–6987 (2009).
(
10.1021/bi900641c
) / Biochemistry / The core signaling proteins of bacterial chemotaxis assemble to form an ultrastable complex by Erbse AH (2009) -
RP Alexander, AC Lowenthal, RM Harshey, KM Ottemann, CheV: CheW-like coupling proteins at the core of the chemotaxis signaling network. Trends Microbiol 18, 494–503 (2010).
(
10.1016/j.tim.2010.07.004
) / Trends Microbiol / CheV: CheW-like coupling proteins at the core of the chemotaxis signaling network by Alexander RP (2010) -
JP Goldman, MD Levin, D Bray, Signal amplification in a lattice of coupled protein kinases. Mol Biosyst 5, 1853–1859 (2009).
(
10.1039/b903397a
) / Mol Biosyst / Signal amplification in a lattice of coupled protein kinases by Goldman JP (2009) -
A Briegel, M Beeby, M Thanbichler, GJ Jensen, Activated chemoreceptor arrays remain intact and hexagonally packed. Mol Microbiol 82, 748–757 (2011).
(
10.1111/j.1365-2958.2011.07854.x
) / Mol Microbiol / Activated chemoreceptor arrays remain intact and hexagonally packed by Briegel A (2011) -
JE Karlinsey, λ-red genetic engineering in Salmonella enterica serovar Typhimurium. Methods Enzymol 421, 199–209 (2007).
(
10.1016/S0076-6879(06)21016-4
) / Methods Enzymol / λ-red genetic engineering in Salmonella enterica serovar Typhimurium by Karlinsey JE (2007) -
M Erhardt, KT Hughes, C-ring requirement in flagellar type III secretion is bypassed by FlhDC upregulation. Mol Microbiol 75, 376–393 (2010).
(
10.1111/j.1365-2958.2009.06973.x
) / Mol Microbiol / C-ring requirement in flagellar type III secretion is bypassed by FlhDC upregulation by Erhardt M (2010) -
CE Wozniak, C Lee, KT Hughes, T-POP array identifies EcnR and PefI-SrgD as novel regulators of flagellar gene expression. J Bacteriol 191, 1498–1508 (2009).
(
10.1128/JB.01177-08
) / J Bacteriol / T-POP array identifies EcnR and PefI-SrgD as novel regulators of flagellar gene expression by Wozniak CE (2009) -
CV Iancu, et al., Electron cryotomography sample preparation using the Vitrobot. Nat Protoc 1, 2813–2819 (2007).
(
10.1038/nprot.2006.432
) / Nat Protoc / Electron cryotomography sample preparation using the Vitrobot by Iancu CV (2007) -
W Tivol, A Briegel, GJ Jensen, An improved cryogen for plunge freezing. Microsc Microanal 14, 375–379 (2008).
(
10.1017/S1431927608080781
) / Microsc Microanal / An improved cryogen for plunge freezing by Tivol W (2008) -
C Suloway, et al., Fully automated, sequential tilt-series acquisition with Leginon. J Struct Biol 167, 11–18 (2009).
(
10.1016/j.jsb.2009.03.019
) / J Struct Biol / Fully automated, sequential tilt-series acquisition with Leginon by Suloway C (2009) -
DN Mastronarde, Automated electron microscope tomography using robust prediction of specimen movements. J Struct Biol 152, 36–51 (2005).
(
10.1016/j.jsb.2005.07.007
) / J Struct Biol / Automated electron microscope tomography using robust prediction of specimen movements by Mastronarde DN (2005) -
JI Agulleiro, JJ Fernandez, Fast tomographic reconstruction on multicore computers. Bioinformatics 27, 582–583 (2011).
(
10.1093/bioinformatics/btq692
) / Bioinformatics / Fast tomographic reconstruction on multicore computers by Agulleiro JI (2011) -
D Nicastro, et al., The molecular architecture of axonemes revealed by cryoelectron tomography. Science 313, 944–948 (2006).
(
10.1126/science.1128618
) / Science / The molecular architecture of axonemes revealed by cryoelectron tomography by Nicastro D (2006) -
Z Otwinowski, W Minor, Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276, 307–326 (1997).
(
10.1016/S0076-6879(97)76066-X
) / Methods Enzymol / Processing of X-ray diffraction data collected in oscillation mode by Otwinowski Z (1997) -
AJ McCoy, et al., Phaser crystallographic software. J Appl Crystallogr 40, 658–674 (2007).
(
10.1107/S0021889807021206
) / J Appl Crystallogr / Phaser crystallographic software by McCoy AJ (2007) -
D McRee, M Israel, XtalView, protein structure solution and protein graphics, a short history. J Struct Biol 163, 208–213 (2008).
(
10.1016/j.jsb.2008.02.004
) / J Struct Biol / XtalView, protein structure solution and protein graphics, a short history by McRee D (2008) -
GF Schröder, AT Brunger, M Levitt, Combining efficient conformational sampling with a deformable elastic network model facilitates structure refinement at low resolution. Structure 15, 1630–1641 (2007).
(
10.1016/j.str.2007.09.021
) / Structure / Combining efficient conformational sampling with a deformable elastic network model facilitates structure refinement at low resolution by Schröder GF (2007) -
GF Schröder, M Levitt, AT Brunger, Super-resolution biomolecular crystallography with low-resolution data. Nature 464, 1218–1222 (2010).
(
10.1038/nature08892
) / Nature / Super-resolution biomolecular crystallography with low-resolution data by Schröder GF (2010) -
AT Brunger, Version 1.2 of the Crystallography and NMR System. Nat Protoc 2, 2728–2788 (2007).
(
10.1038/nprot.2007.406
) / Nat Protoc / Version 1.2 of the Crystallography and NMR System by Brunger AT (2007) -
A Vu, X Wang, H Zhou, FW Dahlquist, The receptor CheW binding interface in bacterial chemotaxis. J Mol Biol 415, 759–767 (2012).
(
10.1016/j.jmb.2011.11.043
) / J Mol Biol / The receptor CheW binding interface in bacterial chemotaxis by Vu A (2012)
Dates
Type | When |
---|---|
Created | 13 years, 6 months ago (Feb. 21, 2012, 10:21 p.m.) |
Deposited | 3 years, 2 months ago (June 7, 2022, 4:33 a.m.) |
Indexed | 1 week, 2 days ago (Aug. 12, 2025, 6:06 p.m.) |
Issued | 13 years, 6 months ago (Feb. 21, 2012) |
Published | 13 years, 6 months ago (Feb. 21, 2012) |
Published Online | 13 years, 6 months ago (Feb. 21, 2012) |
Published Print | 13 years, 5 months ago (March 6, 2012) |
@article{Briegel_2012, title={Bacterial chemoreceptor arrays are hexagonally packed trimers of receptor dimers networked by rings of kinase and coupling proteins}, volume={109}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1115719109}, DOI={10.1073/pnas.1115719109}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Briegel, Ariane and Li, Xiaoxiao and Bilwes, Alexandrine M. and Hughes, Kelly T. and Jensen, Grant J. and Crane, Brian R.}, year={2012}, month=feb, pages={3766–3771} }