Polar chemoreceptor clustering by coupled trimers of dimers.

Receptors of bacterial chemotaxis form clusters at the cell poles, where clusters act as "antennas" to amplify small changes in ligand concentration. It is worthy of note that chemoreceptors cluster at multiple length scales. At the smallest scale, receptors form dimers, which assemble into stable timers of dimers. At a large scale, trimers form large polar clusters composed of thousands of receptors. Although much is known about the signaling properties emerging from receptor clusters, it is unknown how receptors localize at the cell poles and what the determining factors are for cluster size. Here, we present a model of polar receptor clustering based on coupled trimers of dimers, where cluster size is determined as a minimum of the cluster-membrane free energy. This energy has contributions from the cluster-membrane elastic energy, penalizing large clusters due to their high intrinsic curvature, and receptor-receptor coupling that favors large clusters. We find that the reduced cluster-membrane curvature mismatch at the curved cell poles leads to large and robust polar clusters, in line with experimental observation, whereas lateral clusters are efficiently suppressed.

[1]  H. Berg,et al.  Functional interactions between receptors in bacterial chemotaxis , 2004, Nature.

[2]  Sebastian Thiem,et al.  Stochastic assembly of chemoreceptor clusters in Escherichia coli , 2008, Molecular microbiology.

[3]  J. Dubochet,et al.  Cryo-Transmission Electron Microscopy of Frozen-Hydrated Sections of Escherichia coli and Pseudomonas aeruginosa , 2003, Journal of bacteriology.

[4]  M. Manson,et al.  Cooperative signaling among bacterial chemoreceptors. , 2005, Biochemistry.

[5]  Sebastian Thiem,et al.  Protein exchange dynamics at chemoreceptor clusters in Escherichia coli , 2008, Proceedings of the National Academy of Sciences.

[6]  G. L. Hazelbauer,et al.  Accessibility of introduced cysteines in chemoreceptor transmembrane helices reveals boundaries interior to bracketing charged residues , 2004, Protein science : a publication of the Protein Society.

[7]  S. Timoshenko,et al.  Theory of Elasticity (3rd ed.) , 1970 .

[8]  Seifert,et al.  Curvature-induced lateral phase segregation in two-component vesicles. , 1993, Physical review letters.

[9]  L. Kiessling,et al.  Large increases in attractant concentration disrupt the polar localization of bacterial chemoreceptors , 2005, Molecular microbiology.

[10]  William Dowhan,et al.  Visualization of Phospholipid Domains inEscherichia coli by Using the Cardiolipin-Specific Fluorescent Dye 10-N-Nonyl Acridine Orange , 2000, Journal of bacteriology.

[11]  M. Homma,et al.  Stabilization of Polar Localization of a Chemoreceptor via Its Covalent Modifications and Its Communication with a Different Chemoreceptor , 2005, Journal of bacteriology.

[12]  S. Safran,et al.  Effect of lipid characteristics on the structure of transmembrane proteins. , 1998, Biophysical journal.

[13]  S. Subramaniam,et al.  Three-Dimensional Electron Microscopic Imaging of Membrane Invaginations in Escherichia coli Overproducing the Chemotaxis Receptor Tsr , 2004, Journal of bacteriology.

[14]  Rob Phillips,et al.  Membrane-protein interactions in mechanosensitive channels. , 2004, Biophysical journal.

[15]  M. Homma,et al.  Attractant binding alters arrangement of chemoreceptor dimers within its cluster at a cell pole. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  L. Shapiro,et al.  Polar location of the chemoreceptor complex in the Escherichia coli cell. , 1993, Science.

[17]  J. Maddock,et al.  Polar Clustering of the Chemoreceptor Complex inEscherichia coli Occurs in the Absence of Complete CheA Function , 2000, Journal of bacteriology.

[18]  Jemal Guven,et al.  Deformations of the geometry of lipid vesicles , 2002 .

[19]  J. Stock,et al.  Bacterial Chemosensing: Cooperative Molecular Logic , 2004, Current Biology.

[20]  Sebastian Thiem,et al.  Positioning of chemosensory clusters in E. coli and its relation to cell division , 2007, The EMBO journal.

[21]  L. Blayney,et al.  Physical coupling between ryanodine receptor-calcium release channels. , 2005, Journal of molecular biology.

[22]  Gabriela Gonzalez-Bonet,et al.  Reconstruction of the chemotaxis receptor–kinase assembly , 2006, Nature Structural &Molecular Biology.

[23]  X. Xie,et al.  Probing Gene Expression in Live Cells, One Protein Molecule at a Time , 2006, Science.

[24]  Ned S. Wingreen,et al.  A Curvature-Mediated Mechanism for Localization of Lipids to Bacterial Poles , 2006, PLoS Comput. Biol..

[25]  S. Safran,et al.  Interaction between inclusions embedded in membranes. , 1996, Biophysical journal.

[26]  N. Wingreen,et al.  Lipid localization in bacterial cells through curvature-mediated microphase separation. , 2008, Biophysical journal.

[27]  Dennis Bray,et al.  Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis , 2000, Nature Cell Biology.

[28]  H. Huang,et al.  Deformation free energy of bilayer membrane and its effect on gramicidin channel lifetime. , 1986, Biophysical journal.

[29]  Ellen S. Vitetta,et al.  An allosteric model for heterogeneous receptor complexes : Understanding bacterial chemotaxis responses to multiple stimuli , 2006 .

[30]  S. Subramaniam,et al.  Direct visualization of Escherichia coli chemotaxis receptor arrays using cryo-electron microscopy , 2007, Proceedings of the National Academy of Sciences.

[31]  Ned S. Wingreen,et al.  Precise adaptation in bacterial chemotaxis through “assistance neighborhoods” , 2006, Proceedings of the National Academy of Sciences.

[32]  M. Kozlov,et al.  Theory and Phenomenology of Mixed Amphiphilic Aggregates , 1996, cond-mat/9803264.

[33]  M. Reth,et al.  Monomeric and oligomeric complexes of the B cell antigen receptor. , 2000, Immunity.

[34]  Samuel A. Safran,et al.  Membrane-induced interactions between inclusions , 1993 .

[35]  H. Berg,et al.  Osmotic stress mechanically perturbs chemoreceptors in Escherichia coli. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  V. Sourjik,et al.  Spatial organization of the bacterial chemotaxis system. , 2006, Current opinion in microbiology.

[37]  S. Timoshenko,et al.  Theory of elasticity , 1975 .

[38]  J. S. Parkinson,et al.  Crosslinking snapshots of bacterial chemoreceptor squads , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Mingshan Li,et al.  Nanodiscs separate chemoreceptor oligomeric states and reveal their signaling properties. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Judith P Armitage,et al.  The positioning of cytoplasmic protein clusters in bacteria. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Sung-Hou Kim,et al.  Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor , 1999, Nature.

[42]  Reinhard Lipowsky,et al.  Budding of membranes induced by intramembrane domains , 1992 .

[43]  J. S. Parkinson,et al.  Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  J. M. Osborne,et al.  Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk. , 1994, The Journal of biological chemistry.

[45]  B. Bassler,et al.  Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing , 2006, Cell.

[46]  F. Brown Elastic modeling of biomembranes and lipid bilayers. , 2008, Annual review of physical chemistry.

[47]  Terry P Lybrand,et al.  Modeling the transmembrane domain of bacterial chemoreceptors , 2002, Protein science : a publication of the Protein Society.

[48]  Igor B. Zhulin,et al.  Evolutionary genomics reveals conserved structural determinants of signaling and adaptation in microbial chemoreceptors , 2007, Proceedings of the National Academy of Sciences.

[49]  Michio Homma,et al.  Helical distribution of the bacterial chemoreceptor via colocalization with the Sec protein translocation machinery , 2006, Molecular microbiology.

[50]  Ned S. Wingreen,et al.  Chemotaxis Receptor Complexes: From Signaling to Assembly , 2007, PLoS Comput. Biol..

[51]  R. Germain,et al.  The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. , 1999, Annual review of immunology.

[52]  G. L. Hazelbauer,et al.  Cellular Stoichiometry of the Components of the Chemotaxis Signaling Complex , 2004, Journal of bacteriology.

[53]  H. Berg,et al.  Physical responses of bacterial chemoreceptors. , 2007, Journal of molecular biology.

[54]  J. Groves,et al.  Bending mechanics and molecular organization in biological membranes. , 2007, Annual review of physical chemistry.

[55]  M. Homma Chemoreceptor signaling involves dimer-to-dimer interaction with its cluster at a cell pole , 2004 .

[56]  J. Maddock,et al.  Clustering of the Chemoreceptor Complex inEscherichia coli Is Independent of the Methyltransferase CheR and the Methylesterase CheB , 1999, Journal of bacteriology.

[57]  Jason E. Gestwicki,et al.  Evolutionary Conservation of Methyl-Accepting Chemotaxis Protein Location in Bacteria andArchaea , 2000, Journal of bacteriology.

[58]  Rob Phillips,et al.  Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions , 2007, PLoS Comput. Biol..

[59]  Leslie C. Griffith Receptor Clustering: Nothing Succeeds Like Success , 2004, Current Biology.

[60]  A. Holzenburg,et al.  TEM Anaysis of Chemoreceptor Arrays in Native Membranes of E. coli , 2004, Microscopy and Microanalysis.

[61]  S. Subramaniam,et al.  Electron Microscopic Analysis of Membrane Assemblies Formed by the Bacterial Chemotaxis Receptor Tsr , 2003, Journal of bacteriology.

[62]  Yu-Ling Shih,et al.  The MreB and Min cytoskeletal‐like systems play independent roles in prokaryotic polar differentiation , 2005, Molecular microbiology.

[63]  H. Berg,et al.  Effect of Chemoreceptor Modification on Assembly and Activity of the Receptor-Kinase Complex in Escherichia coli , 2004, Journal of bacteriology.

[64]  D E Koshland,et al.  A piston model for transmembrane signaling of the aspartate receptor. , 1999, Science.

[65]  Monica L. Skoge,et al.  Chemosensing in Escherichia coli: two regimes of two-state receptors. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[66]  A. Holzenburg,et al.  Identification of Tsr and Tar Chemoreceptor Arrays in E. coli Inner Membranes , 2005, Microscopy and Microanalysis.

[67]  H. Berg,et al.  Receptor sensitivity in bacterial chemotaxis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Goulian,et al.  Energetics of inclusion-induced bilayer deformations. , 1998, Biophysical journal.

[69]  J. S. Parkinson,et al.  Collaborative signaling by mixed chemoreceptor teams in Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[70]  R. B. Jensen,et al.  Location and architecture of the Caulobacter crescentus chemoreceptor array , 2008, Molecular microbiology.

[71]  J. Falke,et al.  Side chains at the membrane-water interface modulate the signaling state of a transmembrane receptor. , 2004, Biochemistry.

[72]  H. Berg,et al.  Localization of components of the chemotaxis machinery of Escherichia coli using fluorescent protein fusions , 2000, Molecular microbiology.

[73]  W. Boos,et al.  The Tsr chemosensory transducer of Escherichia coli assembles into the cytoplasmic membrane via a SecA-dependent process. , 1988, The Journal of biological chemistry.

[74]  M. Manson,et al.  Tuning a bacterial chemoreceptor with protein-membrane interactions. , 2006, Biochemistry.

[75]  Sung-Hou Kim,et al.  Dynamic and clustering model of bacterial chemotaxis receptors: Structural basis for signaling and high sensitivity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Irene A. Stegun,et al.  Handbook of Mathematical Functions. , 1966 .

[77]  Monica L. Skoge,et al.  Receptor-receptor coupling in bacterial chemotaxis: evidence for strongly coupled clusters. , 2006, Biophysical journal.

[78]  Sebastian Thiem,et al.  Determinants of chemoreceptor cluster formation in Escherichia coli , 2006, Molecular microbiology.

[79]  R. Weis,et al.  Covalent Modification Regulates Ligand Binding to Receptor Complexes in the Chemosensory System of Escherichia coli , 2000, Cell.

[80]  D. Bray,et al.  Receptor clustering as a cellular mechanism to control sensitivity , 1998, Nature.