Do Plants Contain G Protein-Coupled Receptors? 1(C)(W)(OPEN)

Whether G protein-coupled receptors (GPCRs) exist in plants is a fundamental biological question. Interest in deorphanizing new GPCRs arises because of their importance in signaling. Within plants, this is controversial, as genome analysis has identified 56 putative GPCRs, includingGprotein-coupled receptor1 (GCR1), which is reportedly a remote homolog to class A, B, and EGPCRs. Of these, GCR2 is not a GPCR;more recently, it has been proposed that none are, not even GCR1.We have addressed this disparity between genome analysis and biological evidence through a structural bioinformatics study, involving fold recognition methods, fromwhich onlyGCR1 emerges as a strong candidate. To further probeGCR1,wehave developed anovel helix-alignmentmethod, which has been benchmarked against the class A-class B-class F GPCR alignments. In addition, we have presented a mutually consistent set of alignments ofGCR1homologs to classA, class B, and class FGPCRsand shown thatGCR1 is closer to classAand/or class B GPCRs than class A, class B, or class F GPCRs are to each other. To further probe GCR1, we have aligned transmembrane helix 3 of GCR1 to each of the sixGPCR classes. Variability comparisons provide additional evidence that GCR1 homologs have the GPCR fold. From the alignments and a GCR1 comparative model, we have identifiedmotifs that are common to GCR1, class A, B, and E GPCRs. We discuss the possibilities that emerge from this controversial evidence that GCR1 has a GPCR fold.

[1]  David E. Gloriam,et al.  GPCRdb: an information system for G protein-coupled receptors , 2015, Nucleic Acids Res..

[2]  Christopher J. R. Illingworth,et al.  Identifying subset errors in multiple sequence alignments , 2014, Journal of biomolecular structure & dynamics.

[3]  C. Reynolds,et al.  The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach , 2013, Journal of The Royal Society Interface.

[4]  Ali Jazayeri,et al.  Structure of class B GPCR corticotropin-releasing factor receptor 1 , 2013, Nature.

[5]  Chris de Graaf,et al.  Structure of the human glucagon class B G-protein-coupled receptor , 2013, Nature.

[6]  Alan M. Jones,et al.  Eukaryotic G Protein Signaling Evolved to Require G Protein–Coupled Receptors for Activation , 2013, Science Signaling.

[7]  Bryan L. Roth,et al.  Structure of the human smoothened receptor bound to an antitumour agent , 2013, Nature.

[8]  K. Gregory,et al.  Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a “Molecular Switch” in PAM Pharmacology , 2013, Molecular Pharmacology.

[9]  S. Nair,et al.  Crystal Structure of Arabidopsis GCR2 , 2013 .

[10]  René Staritzbichler,et al.  Alignment of Helical Membrane Protein Sequences Using AlignMe , 2013, PloS one.

[11]  Alan M. Jones,et al.  Heterotrimeric G protein signalling in the plant kingdom , 2013, Open Biology.

[12]  M. Babu,et al.  Molecular signatures of G-protein-coupled receptors , 2013, Nature.

[13]  Bruck Taddese,et al.  Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies , 2013, Journal of The Royal Society Interface.

[14]  Alan M. Jones,et al.  “Round Up the Usual Suspects”: A Comment on Nonexistent Plant G Protein-Coupled Receptors1[C][W] , 2013, Plant Physiology.

[15]  R. Stevens,et al.  Structure-function of the G protein-coupled receptor superfamily. , 2013, Annual review of pharmacology and toxicology.

[16]  M. Kojima.  Faculty Opinions recommendation of Structure of the agonist-bound neurotensin receptor. , 2012 .

[17]  Ron O. Dror,et al.  High-resolution crystal structure of human Protease-Activated Receptor 1 bound to the antagonist vorapaxar , 2012, Nature.

[18]  R. Stevens,et al.  Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions , 2012, Science.

[19]  Alan M. Jones,et al.  G Protein Activation without a GEF in the Plant Kingdom , 2012, PLoS genetics.

[20]  Terri K. Attwood,et al.  The PRINTS database: a fine-grained protein sequence annotation and analysis resource—its status in 2012 , 2012, Database J. Biol. Databases Curation.

[21]  Graham J. G. Upton,et al.  G-protein-coupled receptor dynamics: dimerization and activation models compared with experiment. , 2012, Biochemical Society transactions.

[22]  R. Legendre,et al.  Evolution of class A G-protein-coupled receptors: implications for molecular modeling. , 2012, Current medicinal chemistry.

[23]  R. Stevens,et al.  Crystal Structure of a Lipid G Protein–Coupled Receptor , 2012, Science.

[24]  T. Veenstra,et al.  A Gβγ effector, ElmoE, transduces GPCR signaling to the actin network during chemotaxis. , 2012, Developmental cell.

[25]  M. S. Almén,et al.  The Origin of GPCRs: Identification of Mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in Fungi , 2012, PloS one.

[26]  A. Kruse,et al.  Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist , 2011, Nature.

[27]  K. Coopman,et al.  Residues within the transmembrane domain of the glucagon-like peptide-1 receptor involved in ligand binding and receptor activation: modelling the ligand-bound receptor. , 2011, Molecular endocrinology.

[28]  J. Simms,et al.  Lifting the lid on GPCRs: the role of extracellular loops , 2011, British journal of pharmacology.

[29]  Ruben Abagyan,et al.  Structure of the human histamine H1 receptor complex with doxepin , 2011, Nature.

[30]  Jonathan S. Mason,et al.  Progress in Structure Based Drug Design for G Protein-Coupled Receptors , 2011, Journal of medicinal chemistry.

[31]  Richard A Friesner,et al.  Successful prediction of the intra- and extracellular loops of four G-protein-coupled receptors , 2011, Proceedings of the National Academy of Sciences.

[32]  R. Lefkowitz,et al.  Therapeutic potential of β-arrestin- and G protein-biased agonists. , 2011, Trends in molecular medicine.

[33]  Alan M. Jones,et al.  The Crystal Structure of a Self-Activating G Protein α Subunit Reveals Its Distinct Mechanism of Signal Initiation , 2011, Science Signaling.

[34]  C. Malbon.  Wnt signalling: the case of the 'missing' G-protein. , 2011, The Biochemical journal.

[35]  Rachel Hanna,et al.  Phospholipase D controls Dictyostelium development by regulating G protein signaling. , 2011, Cellular signalling.

[36]  V. Katanaev,et al.  Wnt3a stimulation elicits G-protein-coupled receptor properties of mammalian Frizzled proteins. , 2011, The Biochemical journal.

[37]  Jonathan A. Javitch,et al.  Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist , 2010, Science.

[38]  R. Abagyan,et al.  Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists , 2010, Science.

[39]  Gianni De Fabritiis,et al.  Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors , 2010, PLoS Comput. Biol..

[40]  Keshava Rajagopal,et al.  Teaching old receptors new tricks: biasing seven-transmembrane receptors , 2010, Nature Reviews Drug Discovery.

[41]  R. Lefkowitz,et al.  β-arrestin- but not G protein-mediated signaling by the “decoy” receptor CXCR7 , 2009, Proceedings of the National Academy of Sciences.

[42]  Susumu Goto,et al.  KEGG for representation and analysis of molecular networks involving diseases and drugs , 2009, Nucleic Acids Res..

[43]  Marcin J. Skwark,et al.  Sequence analysis SPOCTOPUS: a combined predictor of signal peptides and membrane protein topology , 2008 .

[44]  D. Siderovski,et al.  A sweet cycle for Arabidopsis G-proteins , 2008, Plant signaling & behavior.

[45]  R. Stevens,et al.  The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist , 2008, Science.

[46]  Arne Elofsson,et al.  OCTOPUS: improving topology prediction by two-track ANN-based preference scores and an extended topological grammar , 2008, Bioinform..

[47]  Sitao Wu,et al.  MUSTER: Improving protein sequence profile–profile alignments by using multiple sources of structure information , 2008, Proteins.

[48]  Sarah M Assmann,et al.  Whole proteome identification of plant candidate G-protein coupled receptors in Arabidopsis, rice, and poplar: computational prediction and in-vivo protein coupling , 2008, Genome Biology.

[49]  Gebhard F. X. Schertler,et al.  Structure of a β1-adrenergic G-protein-coupled receptor , 2008, Nature.

[50]  H. Schiöth,et al.  Structural diversity of G protein-coupled receptors and significance for drug discovery , 2008, Nature Reviews Drug Discovery.

[51]  Christopher J. R. Illingworth,et al.  Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR? , 2008, Biophysical chemistry.

[52]  Michael J E Sternberg,et al.  Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre , 2008, Proteins.

[53]  Alan M. Jones,et al.  GTPase acceleration as the rate-limiting step in Arabidopsis G protein-coupled sugar signaling , 2007, Proceedings of the National Academy of Sciences.

[54]  Anna Tramontano,et al.  Critical assessment of methods of protein structure prediction—Round VII , 2007, Proteins.

[55]  R. Abagyan,et al.  Molecular Approximations between Residues 21 and 23 of Secretin and Its Receptor: Development of a Model for Peptide Docking with the Amino Terminus of the Secretin Receptor , 2007, Molecular Pharmacology.

[56]  Christopher J. R. Illingworth,et al.  Computational studies of Family A and Family B GPCRs. , 2007, Biochemical Society transactions.

[57]  Sitao Wu,et al.  LOMETS: A local meta-threading-server for protein structure prediction , 2007, Nucleic acids research.

[58]  Wei-Hua Wu,et al.  A G Protein-Coupled Receptor Is a Plasma Membrane Receptor for the Plant Hormone Abscisic Acid , 2007, Science.

[59]  C. McKerlie,et al.  C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a , 2007, Nature.

[60]  David T. Jones,et al.  Improving the accuracy of transmembrane protein topology prediction using evolutionary information , 2007, Bioinform..

[61]  Alan M. Jones,et al.  Mining the Arabidopsis thaliana genome for highly-divergent seven transmembrane receptors , 2006, Genome Biology.

[62]  Ben M. Webb,et al.  Comparative Protein Structure Modeling Using Modeller , 2006, Current protocols in bioinformatics.

[63]  Erik Granseth,et al.  Structural classification and prediction of reentrant regions in alpha-helical transmembrane proteins: application to complete genomes. , 2006, Journal of molecular biology.

[64]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[65]  Toshio Shimizu,et al.  How accurately can we discriminate G-protein-coupled receptors as 7-tms TM protein sequences from other sequences? , 2005, Biochemical and biophysical research communications.

[66]  Martin Ebeling,et al.  An Automated System for the Analysis of G Protein-Coupled Receptor Transmembrane Binding Pockets: Alignment, Receptor-Based Pharmacophores, and Their Application , 2005, J. Chem. Inf. Model..

[67]  T. Schwartz,et al.  High Constitutive Activity of a Virus-Encoded Seven Transmembrane Receptor in the Absence of the Conserved DRY Motif (Asp-Arg-Tyr) in Transmembrane Helix 3 , 2005, Molecular Pharmacology.

[68]  L. Eichinger,et al.  Manifestations of multicellularity: Dictyostelium reports in. , 2005, Trends in genetics : TIG.

[69]  V. Hornak,et al.  Comparison of class A and D G protein-coupled receptors: common features in structure and activation. , 2005, Biochemistry.

[70]  Johannes Söding,et al.  The HHpred interactive server for protein homology detection and structure prediction , 2005, Nucleic Acids Res..

[71]  Guang R. Gao,et al.  An improved hidden Markov model for transmembrane protein detection and topology prediction and its applications to complete genomes , 2005, Bioinform..

[72]  Alan M. Jones,et al.  GCR1 Can Act Independently of Heterotrimeric G-Protein in Response to Brassinosteroids and Gibberellins in Arabidopsis Seed Germination1[w] , 2004, Plant Physiology.

[73]  S. Assmann,et al.  The Arabidopsis Putative G Protein–Coupled Receptor GCR1 Interacts with the G Protein α Subunit GPA1 and Regulates Abscisic Acid Signaling , 2004, The Plant Cell Online.

[74]  Didier Rognan,et al.  High-Throughput Modeling of Human G-Protein Coupled Receptors: Amino Acid Sequence Alignment, Three-Dimensional Model Building, and Receptor Library Screening , 2004, J. Chem. Inf. Model..

[75]  R. Wolf,et al.  Homology Modeling of the Transmembrane Domain of the Human Calcium Sensing Receptor and Localization of an Allosteric Binding Site* , 2004, Journal of Biological Chemistry.

[76]  Geoffrey J. Barton,et al.  The Jalview Java alignment editor , 2004, Bioinform..

[77]  J. Krause,et al.  C5L2, a nonsignaling C5A binding protein. , 2003, Biochemistry.

[78]  H. Schiöth,et al.  The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. , 2003, Molecular pharmacology.

[79]  Liam J. McGuffin,et al.  Improvement of the GenTHREADER Method for Genomic Fold Recognition , 2003, Bioinform..

[80]  A. Krogh,et al.  Reliability measures for membrane protein topology prediction algorithms. , 2003, Journal of molecular biology.

[81]  István Simon,et al.  The HMMTOP transmembrane topology prediction server , 2001, Bioinform..

[82]  Rolf Apweiler,et al.  Evaluation of methods for the prediction of membrane spanning regions , 2001, Bioinform..

[83]  T L Blundell,et al.  FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. , 2001, Journal of molecular biology.

[84]  P. Devreotes,et al.  Receptor-Mediated Activation of Heterotrimeric G-Proteins in Living Cells , 2001, Science.

[85]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[86]  Jorja G. Henikoff,et al.  PHAT: a transmembrane-specific substitution matrix , 2000, Bioinform..

[87]  K. Palczewski,et al.  Crystal structure of rhodopsin: A G protein-coupled receptor. , 2000, Science.

[88]  D T Jones,et al.  Protein secondary structure prediction based on position-specific scoring matrices. , 1999, Journal of molecular biology.

[89]  O. Lichtarge,et al.  Similar structures and shared switch mechanisms of the beta2-adrenoceptor and the parathyroid hormone receptor. Zn(II) bridges between helices III and VI block activation. , 1999, The Journal of biological chemistry.

[90]  T. Frimurer,et al.  Structure of the integral membrane domain of the GLP1 receptor , 1999, Proteins.

[91]  R. Hooley.  A role for G proteins in plant hormone signalling , 1999 .

[92]  David C. Jones,et al.  GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences. , 1999, Journal of molecular biology.

[93]  J. Bockaert,et al.  Molecular tinkering of G protein‐coupled receptors: an evolutionary success , 1999, The EMBO journal.

[94]  G. Tusnády,et al.  Principles governing amino acid composition of integral membrane proteins: application to topology prediction. , 1998, Journal of molecular biology.

[95]  D. Dymock,et al.  A higher plant seven-transmembrane receptor that influences sensitivity to cytokinins , 1998, Current Biology.

[96]  L. Josefsson,et al.  Cloning of a putative G-protein-coupled receptor from Arabidopsis thaliana. , 1997, European journal of biochemistry.

[97]  J. Baldwin,et al.  An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. , 1997, Journal of molecular biology.

[98]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[99]  Manuel G. Claros,et al.  TopPred II: an improved software for membrane protein structure predictions , 1994, Comput. Appl. Biosci..

[100]  W R Taylor,et al.  A model recognition approach to the prediction of all-helical membrane protein structure and topology. , 1994, Biochemistry.

[101]  T K Attwood,et al.  Fingerprinting G-protein-coupled receptors. , 1994, Protein engineering.

[102]  S Henikoff,et al.  Performance evaluation of amino acid substitution matrices , 1993, Proteins.

[103]  D. T. Jones,et al.  A new approach to protein fold recognition , 1992, Nature.

[104]  Lisa M Simpson,et al.  Modeling active GPCR conformations. , 2013, Methods in enzymology.

[105]  A. Lesk.  Introduction to bioinformatics , 2002 .

[106]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[107]  David T. Jones.  THREADER : Protein Sequence Threading by Double Dynamic Programming , 1998 .

[108]  J. Ballesteros,et al.  [19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors , 1995 .

[109]  J Hoflack,et al.  Re-evaluation of bacteriorhodopsin as a model for G protein-coupled receptors. , 1994, Trends in pharmacological sciences.

[110]  Kolakowski Lf.  GCRDB: A G-PROTEIN-COUPLED RECEPTOR DATABASE , 1994 .

[111]  S. Trumpp-Kallmeyer,et al.  This is not a G protein-coupled receptor. , 1993, Trends in pharmacological sciences.

[112]  R. Doolittle.  Of urfs and orfs : a primer on how to analyze devised amino acid sequences , 1986 .

[113]  C. Chuong,et al.  Article type Software , 2007 .