Etude structurale des cassures d'hélices et son application à la modélisation des récepteurs couplés aux protéines G (RCPG). (Structural study of kelix kinks and its application to modeling G protein coupled receptors (RCPG))

α-Helices are the most common secondary structures found in globular proteins. In this repo rt, we analyze the stereochemical and sequence properties of helix-X-helix motifs in which two αhelices are linked by a single residue, in search o f characteristic structures and sequence signals. The analysis is carried out on a database of 837 nonredundant helix-X-helix motifs. The kinks are characterized by the bend angle between the axes of the N-terminal and C-terminal helices and the wobble angle corresponding to the rotation of Cterminal helix axis on the plane perpendicular to t he N-terminal one. The phi-psi dihedral angles of the linker residue are clustered in six distinct areas of the Ramachandran plot: two areas are located in the additional allowed alpha region ( α1 and α2), two areas are in the additional allowed beta region ( β1 and β2) and two areas have a positive phi values ( αL and βM). Each phi/psi region corresponds to characteristic bend and wobble angles and amino acid distributions. Bend angles can vary from 0 to 160°. Most wobble angles correspond to a counterclockwise rotation of the C-terminal helix. Proline residues are rigorously excluded from the linker position X but have a high propensity at position X+1 of the β1 and β2 motifs (12 and 7, respectively) and at position X+3 of the α1 motifs (9). Glycine linkers are located either in the αL region (20%) or in the βM region (80%). This latter conformation is characterized by a marked bend angle (124 ± 18°) and a clockwise wobble. Among other amino acids, Asn is remarkable for its high propensity (>3) at t he linker position of the α2, β1 and β2 motifs. Stabilization of HXH motifs by H-bonds between polar side chains of the linker and polar groups of the backbone is determined. A method based on position-specific scoring matrices is developed for conformational prediction. The accuracy of the predictions reaches 80% when the method is applied to Proline-induced kinks or to kinks with bend angles in the 50°-100° range.

[1]  Krzysztof Palczewski,et al.  Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin. , 2003, Biochemistry.

[2]  A. Scheer,et al.  Constitutively active mutants of the alpha 1B‐adrenergic receptor: role of highly conserved polar amino acids in receptor activation. , 1996, The EMBO journal.

[3]  C. Ramakrishnan,et al.  Deterministic features of side-chain main-chain hydrogen bonds in globular protein structures. , 2000, Protein engineering.

[4]  B. Rost,et al.  Improved prediction of protein secondary structure by use of sequence profiles and neural networks. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Ramakumar,et al.  π‐Turns in proteins and peptides: Classification, conformation, occurrence, hydration and sequence , 1996, Protein science : a publication of the Protein Society.

[6]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[7]  T. Unger,et al.  Vasoactive peptides, their receptors and drug development. , 2004, Basic & clinical pharmacology & toxicology.

[8]  A. Valencia,et al.  Practical limits of function prediction , 2000, Proteins.

[9]  T. Okada,et al.  Local peptide movement in the photoreaction intermediate of rhodopsin , 2006, Proceedings of the National Academy of Sciences.

[10]  International Human Genome Sequencing Consortium.  Initial sequencing and analysis of the human genome , 2001, Nature.

[11]  G. N. Ramachandran,et al.  Stereochemical criteria for polypeptide and protein chain conformations. 3. Helical and hydrogen-bonded polypeptide chains. , 1966, Biophysical journal.

[12]  P. Y. Chou,et al.  Prediction of the secondary structure of proteins from their amino acid sequence. , 2006 .

[13]  Roger E. Moore,et al.  Qscore: An algorithm for evaluating SEQUEST database search results , 2002, Journal of the American Society for Mass Spectrometry.

[14]  P. Argos,et al.  Seventy‐five percent accuracy in protein secondary structure prediction , 1997, Proteins.

[15]  J. Farber,et al.  Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. , 1999, Annual review of immunology.

[16]  Manfred Burghammer,et al.  Crystal structure of a thermally stable rhodopsin mutant. , 2007, Journal of molecular biology.

[17]  Bosco K. Ho,et al.  The Ramachandran plots of glycine and pre-proline , 2005, BMC Structural Biology.

[18]  G. N. Ramachandran,et al.  Stereochemistry of polypeptide chain configurations. , 1963, Journal of molecular biology.

[19]  R. Aurora,et al.  Helix capping , 1998, Protein science : a publication of the Protein Society.

[20]  J. Bockaert,et al.  [Use of a G-protein-coupled receptor to communicate. An evolutionary success]. , 1998, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[21]  W. DeGrado,et al.  A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. , 1990, Science.

[22]  Peter C. Kahn,et al.  Defining the axis of a helix , 1989, Comput. Chem..

[23]  K. Palczewski,et al.  Crystal Structure of Rhodopsin: A G‐Protein‐Coupled Receptor , 2002, Chembiochem : a European journal of chemical biology.

[24]  R D Smith,et al.  Angiotensin II receptor subtypes. , 1992, American journal of hypertension.

[25]  L. F. Kolakowski.  GCRDb: a G-protein-coupled receptor database. , 1994, Receptors & channels.

[26]  A. Methner,et al.  Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands , 2002, Genome Biology.

[27]  A. Spiegel,et al.  Mutations in G proteins and G protein-coupled receptors in endocrine disease. , 1996, The Journal of clinical endocrinology and metabolism.

[28]  P. Argos,et al.  Knowledge‐based protein secondary structure assignment , 1995, Proteins.

[29]  U. Hobohm,et al.  Enlarged representative set of protein structures , 1994, Protein science : a publication of the Protein Society.

[30]  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.

[31]  F. Richards,et al.  Identification of structural motifs from protein coordinate data: Secondary structure and first‐level supersecondary structure * , 1988, Proteins.

[32]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[33]  P. Y. Chou,et al.  Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. , 1974, Biochemistry.

[34]  R. Doms,et al.  CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. , 1999, Blood.

[35]  Baldomero Oliva,et al.  Structural similarity to link sequence space: New potential superfamilies and implications for structural genomics , 2002, Protein science : a publication of the Protein Society.

[36]  Slawomir K. Grzechnik,et al.  Crystal structure of O‐acetylserine sulfhydrylase (TM0665) from Thermotoga maritima at 1.8 Å resolution , 2004, Proteins: Structure, Function, and Bioinformatics.

[37]  F. Cordes,et al.  Proline-induced distortions of transmembrane helices. , 2002, Journal of molecular biology.

[38]  H. Luecke,et al.  Structural and functional characterization of pi bulges and other short intrahelical deformations. , 2004, Structure.

[39]  J. Ballesteros,et al.  Activation of the β2-Adrenergic Receptor Involves Disruption of an Ionic Lock between the Cytoplasmic Ends of Transmembrane Segments 3 and 6* , 2001, The Journal of Biological Chemistry.

[40]  P. Timmermans,et al.  Identification of angiotensin II receptor subtypes. , 1989, Biochemical and biophysical research communications.

[41]  J M Thornton,et al.  Assessment of conformational parameters as predictors of limited proteolytic sites in native protein structures. , 1998, Protein engineering.

[42]  L. Pardo,et al.  Serine and threonine residues bend alpha-helices in the chi(1) = g(-) conformation. , 2000, Biophysical journal.

[43]  S. Kumar,et al.  Geometrical and sequence characteristics of alpha-helices in globular proteins. , 1998, Biophysical journal.

[44]  Ian W. Davis,et al.  Structure validation by Cα geometry: ϕ,ψ and Cβ deviation , 2003, Proteins.

[45]  K. R. Woods,et al.  Prediction of protein antigenic determinants from amino acid sequences. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[46]  P. Y. Chou,et al.  Prediction of protein conformation. , 1974, Biochemistry.

[47]  J. Richardson,et al.  Amino acid preferences for specific locations at the ends of alpha helices. , 1988, Science.

[48]  D. Eisenberg,et al.  Analysis of membrane and surface protein sequences with the hydrophobic moment plot. , 1984, Journal of molecular biology.

[49]  W. DeGrado,et al.  Analysis and design of turns in alpha-helical hairpins. , 2005, Journal of molecular biology.

[50]  M Ouali,et al.  Cascaded multiple classifiers for secondary structure prediction , 2000, Protein science : a publication of the Protein Society.

[51]  H. Schiöth,et al.  The Repertoire of G-Protein–Coupled Receptors in Fully Sequenced Genomes , 2005, Molecular Pharmacology.

[52]  G J Kleywegt,et al.  Recognition of spatial motifs in protein structures. , 1999, Journal of molecular biology.

[53]  Fabien Cailliez,et al.  Secondary structure assignment that accurately reflects physical and evolutionary characteristics , 2005, BMC Bioinformatics.

[54]  J. Ballesteros,et al.  Structural mimicry in G protein-coupled receptors: implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors. , 2001, Molecular pharmacology.

[55]  L. Pardo,et al.  Design, synthesis and pharmacological evaluation of 5-hydroxytryptamine(1a) receptor ligands to explore the three-dimensional structure of the receptor. , 2002, Molecular pharmacology.

[56]  M. Sternberg,et al.  Left-handed polyproline II helices commonly occur in globular proteins. , 1993, Journal of molecular biology.

[57]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[58]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[59]  J. Rossjohn,et al.  Molecular basis of glutathione synthetase deficiency and a rare gene permutation event , 1999, The EMBO journal.

[60]  Claus Liebmann,et al.  G protein-coupled receptors and their signaling pathways: classical therapeutical targets susceptible to novel therapeutic concepts. , 2004, Current pharmaceutical design.

[61]  D C Teller,et al.  Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). , 2001, Biochemistry.

[62]  U. Hobohm,et al.  Selection of representative protein data sets , 1992, Protein science : a publication of the Protein Society.

[63]  H. A. Nagarajaram,et al.  Stereochemical punctuation marks in protein structures: glycine and proline containing helix stop signals. , 1998, Journal of molecular biology.

[64]  T L Blundell,et al.  Properties of polyproline II, a secondary structure element implicated in protein–protein interactions , 2005, Proteins.

[65]  Krzysztof Palczewski,et al.  The crystallographic model of rhodopsin and its use in studies of other G protein-coupled receptors. , 2003, Annual review of biophysics and biomolecular structure.

[66]  Dominic J. B. Hunter,et al.  Assembly of an oxo-zirconium(IV) cluster in a protein cleft. , 2004, Angewandte Chemie.

[67]  G J Barton,et al.  Evaluation and improvement of multiple sequence methods for protein secondary structure prediction , 1999, Proteins.

[68]  H Weinstein,et al.  Related Contribution of Specific Helix 2 and 7 Residues to Conformational Activation of the Serotonin 5-HT2A Receptor (*) , 1995, The Journal of Biological Chemistry.

[69]  Simon J Hubbard,et al.  Improved prediction for N-termini of alpha-helices using empirical information. , 2004, Proteins.

[70]  A. Savchenko,et al.  Crystal complexes of a predicted S‐adenosylmethionine‐dependent methyltransferase reveal a typical AdoMet binding domain and a substrate recognition domain , 2003, Protein science : a publication of the Protein Society.

[71]  Giorgio Valle,et al.  Simple consensus procedures are effective and sufficient in secondary structure prediction. , 2003, Protein engineering.

[72]  P. Karplus.  Experimentally observed conformation‐dependent geometry and hidden strain in proteins , 1996, Protein science : a publication of the Protein Society.

[73]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[74]  J. Thornton,et al.  Satisfying hydrogen bonding potential in proteins. , 1994, Journal of molecular biology.

[75]  Y. Kaziro,et al.  Molecular cloning and expression of a cDNA encoding the secretin receptor. , 1991, The EMBO journal.

[76]  G von Heijne,et al.  A turn propensity scale for transmembrane helices. , 1999, Journal of molecular biology.

[77]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[78]  Shoshana J. Wodak,et al.  The TXP Motif in the Second Transmembrane Helix of CCR5 , 2001, The Journal of Biological Chemistry.

[79]  L. Pardo,et al.  Ser and Thr residues modulate the conformation of pro-kinked transmembrane alpha-helices. , 2004, Biophysical journal.

[80]  A A Salamov,et al.  Prediction of protein secondary structure by combining nearest-neighbor algorithms and multiple sequence alignments. , 1995, Journal of molecular biology.

[81]  Z. Weng,et al.  Main‐chain conformational tendencies of amino acids , 2005, Proteins.

[82]  J. Thornton,et al.  Helix geometry in proteins. , 1988, Journal of molecular biology.

[83]  P. Yeagle,et al.  A conformational trigger for activation of a G protein by a G protein-coupled receptor. , 2003, Biochemistry.

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

[85]  M. Brunori,et al.  Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium. , 2003, Biochemistry.

[86]  David C. Jones,et al.  CATH--a hierarchic classification of protein domain structures. , 1997, Structure.

[87]  W. DeGrado,et al.  Alpha-alpha linking motifs and interhelical orientations. , 2005, Proteins.

[88]  J. Schanstra,et al.  Participation of transmembrane proline 82 in angiotensin II AT1 receptor signal transduction , 2007, Regulatory Peptides.

[89]  J. Garnier,et al.  Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. , 1978, Journal of molecular biology.

[90]  Manfred Burghammer,et al.  Structure of bovine rhodopsin in a trigonal crystal form. , 2003, Journal of molecular biology.

[91]  Duan Yang,et al.  The evolution of transmembrane helix kinks and the structural diversity of G protein-coupled receptors. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[92]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[93]  W. Kabsch,et al.  How good are predictions of protein secondary structure? , 1983, FEBS letters.

[94]  Joël Pothier,et al.  P-SEA: a new efficient assignment of secondary structure from C alpha trace of proteins , 1997, Comput. Appl. Biosci..

[95]  L. Serrano,et al.  C-capping and helix stability: the Pro C-capping motif. , 1997, Journal of molecular biology.

[96]  W. DeGrado,et al.  Amino acid propensities are position-dependent throughout the length of alpha-helices. , 2004, Journal of molecular biology.

[97]  S. Al-Karadaghi,et al.  Occurrence, conformational features and amino acid propensities for the pi-helix. , 2002, Protein engineering.

[98]  R. Srinivasan,et al.  Rules for alpha-helix termination by glycine. , 1994, Science.

[99]  H. Khorana,et al.  Requirement of Rigid-Body Motion of Transmembrane Helices for Light Activation of Rhodopsin , 1996, Science.

[100]  C. Ramakrishnan,et al.  Secondary structures without backbone: an analysis of backbone mimicry by polar side chains in protein structures. , 1999, Protein engineering.

[101]  U. Gether.  Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. , 2000, Endocrine reviews.

[102]  J. Gibrat,et al.  Protein secondary structure assignment revisited: a detailed analysis of different assignment methods , 2005, BMC Structural Biology.

[103]  Chris Sander,et al.  Removing near-neighbour redundancy from large protein sequence collections , 1998, Bioinform..

[104]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[105]  J. Thornton,et al.  Influence of proline residues on protein conformation. , 1991, Journal of molecular biology.

[106]  Sujata Sharma,et al.  Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis , 2000, Nature Structural Biology.

[107]  Sandeep Kumar,et al.  Dissecting α‐helices: Position‐specific analysis of α‐helices in globular proteins , 1998, Proteins.

[108]  Yoshinori Shichida,et al.  Functional role of internal water molecules in rhodopsin revealed by x-ray crystallography , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[109]  C. Ramakrishnan,et al.  Stereochemical criteria for polypeptide and protein chain conformations , 1964 .

[110]  Krzysztof Palczewski,et al.  Crystal structure of a photoactivated deprotonated intermediate of rhodopsin , 2006, Proceedings of the National Academy of Sciences.

[111]  Marcus Elstner,et al.  The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. , 2004, Journal of molecular biology.

[112]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[113]  D R Flower,et al.  Modelling G-protein-coupled receptors for drug design. , 1999, Biochimica et biophysica acta.

[114]  G J Barton,et al.  Application of multiple sequence alignment profiles to improve protein secondary structure prediction , 2000, Proteins.

[115]  M. Levitt,et al.  Automatic identification of secondary structure in globular proteins. , 1977, Journal of molecular biology.

[116]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[117]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[118]  Sudhir Kumar,et al.  MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment , 2004, Briefings Bioinform..

[119]  J. Thornton,et al.  Structures of N‐termini of helices in proteins , 1997, Protein science : a publication of the Protein Society.