Structural interpretation of P2X receptor mutagenesis studies on drug action

British Journal of Pharmacology

Volumn 161, Issue 5, 2010, Pages 961-971

  Evans, Richard J ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

ATP; Ion channel; Mutagenesis; P2X; Structure function

Indexed keywords

ADENOSINE TRIPHOSPHATE; PURINERGIC P2X RECEPTOR; PURINERGIC P2X4 RECEPTOR; PURINERGIC P2X7 RECEPTOR; PURINERGIC RECEPTOR BLOCKING AGENT; PYRIDOXAL PHOSPHATE 6 AZOPHENYL 2',4' DISULFONIC ACID; SURAMIN;

ALLOSTERISM; BINDING SITE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLIZATION; DISULFIDE BOND; DRUG MECHANISM; GENE INACTIVATION; GENE MUTATION; GENE SILENCING; GLYCOSYLATION; HUMAN; IMMUNOHISTOCHEMISTRY; MUTAGENESIS; PHENOTYPE; PREDICTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION; STOICHIOMETRY; STRUCTURE ANALYSIS; VOLTAGE CLAMP; ZEBRA FISH;

ADENOSINE TRIPHOSPHATE; ALLOSTERIC REGULATION; ANIMALS; BINDING SITES; HUMANS; LIGANDS; MODELS, MOLECULAR; MUTAGENESIS; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTORS, PURINERGIC P2X; RECEPTORS, PURINERGIC P2X4;

EID: 77958610109     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.00728.x     Document Type: Review

References (93)

1. Abbracchio MP, Burnstock G (1994). Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmac Ther 64: 445-475.
2. Acuna-Castillo C, Coddou C, Bull P, Brito J, Huidobro-Toro JP (2007). Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X7 purinergic receptor. J Neurochem 101: 17-26.
3. Adriouch S, Bannas P, Schwarz N, Fliegert R, Guse AH, Seman M et al. (2007). ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J 22: 861-869.
4. Barrera NP, Ormond SJ, Henderson RM, Murrell-Lagnado RD, Edwardson JM (2005). AFM imaging demonstrates that P2X2 receptors are trimers, but that P2X6 receptor subunits do not oligomerize. J Biol Chem 280: 10759-10765.
5. Bean BP (1990). ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. J Neurosci 10: 1-10.
6. Brake AJ, Wagenbach MJ, Julius D (1994). New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature 371: 519-523.
7. Braun K, Rettinger J, Ganso M, Kassack M, Hildebrandt C, Ullmann H et al. (2001). NF449: a subnanomolar potency antagonist at recombinant rat P2X1 receptors. Naunyn Schmiedebergs Arch Pharmacol 364: 285-290.
8. Buell G, Lewis C, Collo G, North RA, Surprenant A (1996). An antagonist-insensitive P2X receptor expressed in epithlia and brain. EMBO J 15: 55-62.
9. Burnstock G (2006a). Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27: 166-176.
10. Burnstock G (2006b). Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58: 58-86.
11. Burnstock G, Kennedy C (1985). Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16: 433-440.
12. Cao L, Broomhead HE, Young MT, North RA (2009). Polar residues in the second transmembrane domain of the rat P2X2 receptor that affect spontaneous gating, unitary conductance, and rectification. J Neurosci 29: 14257-14264.
13. Cao L, Young MT, Broomhead HE, Fountain SJ, North RA (2007). Thr339-to-serine substitution in rat P2X2 receptor second transmembrane domain causes constitutive opening and indicates a gating role for Lys308. J Neurosci 27: 12916-12923.
14. Chen C-C, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN (1995). A P2X purincoeptor expressed by a subset of sensory neurons. Nature 377: 428-431.
15. Clarke CE, Benham CD, Bridges A, George AR, Meadows HJ (2000). Mutation of histidine 286 of the human P2X4 purinoceptor removes extracellular pH sensitivity. J Physiol 523: 697-703.
16. Cloues R, Jones S, Brown DA (1993). Zn2+ potentiates ATP-activated currents in rat sympathetic neurons. Pflugers Arch 424: 152-158.
17. Clyne JD, LaPointe LD, Hume RI (2002a). The role of histidine residues in modulation of the rat P2X(2) purinoceptor by zinc and pH. J Physiol 539: 347-359.
18. Clyne JD, Wang LF, Hume RI (2002b). Mutational analysis of the conserved cysteines of the rat P2X2 purinoceptor. J Neurosci 22: 3873-3880.
19. Coddou C, Acuna-Castillo C, Bull P, Huidobro-Toro JP (2007). Dissecting the facilitator and inhibitor allosteric metal sites of the P2X4 receptor channel: critical roles of Cys-132 for zinc-potentiation and Asp-138 for copper-inhibition. J Biol Chem 282: 36879-36886.
20. Cook SP, Rodland KD, McCleskey EW (1998). A memory for extracellular Ca2+ by speeding recovery of P2X receptors from desensitisation. J Neurosci 18: 9238-9244.
21. Ding S, Sachs F (1999). Single channel properties of P2X2 purinoceptors. J Gen Physiol 113: 695-720.
22. Dubyak GR (1991). Signal transduction by P2-purinergic receptors for extracellular ATP. Am J Respir Cell Mol Biol 4: 295-300.
23. Egan TM, Cox JA, Voigt MM (2004). Molecular structure of P2X receptors. Curr Top Med Chem 4: 821-829.
24. Egan TM, Haines WR, Voigt MM (1998). A domain contributing to the ion channel of ATP-gated P2X2 receptors identified by the substituted cycteine accessibitlity method. J Neurosci 18: 2350-2359.
25. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF et al. (2009). Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461: 282-286.
26. Ennion SJ, Evans RJ (2002). Conserved cysteine residues in the extracellular loop of the human P2X(1) receptor form disulfide bonds and are involved in receptor trafficking to the cell surface. Mol Pharmacol 61: 303-311.
27. Ennion S, Hagan S, Evans RJ (2000). The role of positively charged amino acids in ATP recognition by human P2X1 receptors. J Biol Chem 275: 29361-29367.
28. Ennion SJ, Ritson J, Evans RJ (2001). Conserved negatively charged residues are not required for ATP action at P2X(1) receptors. Biochem Biophys Res Commun 289: 700-704.
29. Evans RJ (2009). Orthosteric and allosteric binding sites of P2X receptors. Eur Biophys J 38: 319-327.
30. Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L et al. (2005). ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310: 1495-1499.
31. Garcia-Guzman M, Soto F, Gomez-Hernandez JM, Lund P-E, Stuhmer W (1997a). Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue. Mol Pharmacol 51: 109-118.
32. Garcia-Guzman M, Soto F, Gomez-Hernandez JM, Lund P-E, Stuhmer W (1997b). Characterization of recombinant human P2X4 receptor reveals pharmacological differences with the rat homologue. Mol Pharmacol 51: 109-118.
33. Gerevich Z, Zadori ZS, Koles L, Kopp L, Milius D, Wirkner K et al. (2007). Dual effect of acid pH on purinergic P2X3 receptors depends on the histidine-206 residue. J Biol Chem 282: 33949-33957.
34. Gonzales EB, Kawate T, Gouaux E (2009). Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460: 599-604.
35. Haines WR, Migita K, Cox JA, Egan TM, Voigt MM (2001a). The first transmembrane domain of the P2X receptor subunit participates in the agonist-induced gating of the channel. J Biol Chem 276: 32793-32798.
36. Haines WR, Voigt MM, Migita K, Torres GE, Egan TE (2001b). On the contribution of the first transmembrane domain to whole-cell current through an ATP-gated ionotropic P2X receptor. J Neurosci 21: 5885-5892.
37. Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ et al. (2002). A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci U S A 99: 17179-17184.
38. Jiang LH, Kim M, Spelta V, Bo X, Surprenant A, North RA (2003). Subunit arrangement in P2X receptors. J Neurosci 23: 8903-8910.
39. Jiang L-H, Rassendren F, Spelta V, Surprenant A, North RA (2001). Amino acid residues involved in gating identified in the first membrane-spanning domain of the rat p2X2 receptor. J Biol Chem 276: 14902-14908.
40. Jiang L-H, Rassendren F, Surprenant A, North RA (2000). Identification of amino acid residues contributing to the ATP binding site of a purinergic P2X receptor. J Biol Chem 275: 34190-34196.
41. Jones CA, Chessell IP, Simon J, Barnard EA, Miller KJ, Michel AD et al. (2000). Functional characterization of the P2X4 receptor orthologues. Br J Pharmacol 129: 388-394.
42. Kawate T, Michel JC, Birdsong WT, Gouaux E (2009). Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460: 592-598.
43. Keceli B, Kubo Y (2009). Functional and structural identification of amino acid residues of the P2X2 receptor channel critical for the voltage- and [ATP]-dependent gating. J Physiol 587: 5801-5818.
44. Kim M, Jiang L-H, Wilson HL, North RA, Surprenant A (2001). Proteomic and functional evidence for a P2X7 receptor signalling complex. EMBO J 20: 6347-6358.
45. Kubo Y, Fujiwara Y, Keceli B, Nakajo K (2009). Dynamic aspects of functional regulation of the ATP receptor channel P2X(2). J Physiol 587: 5317-5324.
46. Lewis CJ, Gitterman DP, Schluter H, Evans RJ (2000). Effects of diadenosine polyphosphates (ApnAs) and adenosine polyphospho guanosines (ApnGs) on rat mesenteric artery P2X receptor ion channels. Br J Pharmacol 129: 124-130.
47. Lewis C, Neidhart S, Holy C, North RA, Buell G, Surprenant A (1995). Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 377: 432-435.
48. Li M, Chang TH, Silberberg SD, Swartz KJ (2008). Gating the pore of P2X receptor channels. Nat Neurosci 11: 883-887.
49. Li C, Peoples RW, Li Z, Weight FF (1993). Zn2+ potentiates excitatory action of ATP on mammalian neurons. Proc Natl Acad Sci U S A 90: 8264-8267.
50. Lorca RA, Coddou C, Gazitua MC, Bull P, Arredondo C, Huidobro-Toro JP (2005). Extracellular histidine residues identify common structural determinants in the copper/zinc P2X2 receptor modulation. J Neurochem 95: 499-512.
51. Marquez-Klaka B, Rettinger J, Bhargava Y, Eisele T, Nicke A (2007). Identification of an intersubunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. J Neurosci 27: 1456-1466.
52. Marquez-Klaka B, Rettinger J, Nicke A (2009). Inter-subunit disulfide cross-linking in homomeric and heteromeric P2X receptors. Eur Biophys J 38: 329-338.
53. Michel AD, Clay WC, Ng SW, Roman S, Thompson K, Condreay JP et al. (2008). Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects. Br J Pharmacol 155: 738-751.
54. Michel AD, Lundstrom K, Buell GN, Surprenant A, Valera S, Humphrey PPA (1996). A comparison of the binding characteristics of recombinant P2X1 and P2X2 receptors. Br J Pharmacol 118: 1806-1812.
55. Mio K, Kubo Y, Ogura T, Yamamoto T, Sato C (2005). Visualization of the trimeric P2X(2) receptor with a crown-capped extracellular domain. Biochem Biophys Res Commun 337: 998-1005.
56. Mio K, Ogura T, Yamamoto T, Hiroaki Y, Fujiyoshi Y, Kubo Y et al. (2009). Reconstruction of the P2X(2) receptor reveals a vase-shaped structure with lateral tunnels above the membrane. Structure 17: 266-275.
57. Nagaya N, Tittle RK, Saar N, Dellal SS, Hume RI (2005). An intersubunit Zn2+ binding site in rat P2X2 receptors. J Biol Chem 280: 25982-25993.
58. Nakazawa K, Liu M, Inoue K, Ohno Y (1997). Potent inhibition by trivalent cations of ATP-gated channels. Eur J Pharmacol 325: 237-243.
59. Nakazawa K, Yamakoshi Y, Tsuchiya T, Ohno Y (2005). Purification and aqueous phase atomic force microscopic observation of recombinant P2X2 receptor. Eur J Pharmacol 518: 107-110.
60. Newbolt A, Stoop R, Virginio C, Surprenant A, North RA, Buell G et al. (1998). Membrane topology of an ATP-gated ion channel (P2X receptor). J Biol Chem 273: 15177-15182.
61. Nicke A, Baumert H, Rettinger J, Eichele A, Lambrecht G, Mutschler E et al. (1998). P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels. EMBO J 17: 3016-3028.
62. North RA (2002). Molecular physiology of P2X receptors. Physiol Rev 82: 1013-1067.
63. North RA, Surprenant A (2000). Pharmacology of cloned P2X receptors. Annu Rev Pharmacol Toxicol 40: 563-580.
64. Pless SA, Lynch JW (2009). Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domain. J Biol Chem 284: 15847-15856.
65. Pratt EB, Brink TS, Bergson P, Voigt MM, Cook SP (2005). Use-dependent inhibition of P2X3 receptors by nanomolar agonist. J Neurosci 25: 7359-7365.
66. Ralevic V, Hoyle CHV, Burnstock G (1995). Pivotal role of phosphate chain length in vasoconstrictor versus vasodilator actions of adenine dinucleotides in rat mesenteric arteries. J Physiol 483: 703-713.
67. Rassendren F, Buell G, Newbolt A, North RA, Surprenant A (1997). Identification of amino acid residues contributing to the pore of a P2X receptor. EMBO J 16: 3446-3454.
68. Rettinger J, Schmalzing G (2004). Desensitization masks nanomolar potency of ATP for the P2X1 receptor. J Biol Chem 279: 6426-6433.
69. Roberts JA, Digby HR, Kara M, Ajouz SE, Sutcliffe MJ, Evans RJ (2008). Cysteine substitution mutagenesis and the effects of methanethiosulfonate reagents at P2X2 and P2X4 receptors support a core common mode of ATP action at P2X receptors. J Biol Chem 283: 20126-20136.
70. Roberts JA, Evans RJ (2004). ATP binding at human P2X1 receptors: contribution of aromatic and basic amino acids revealed using mutagenesis and partial agonists. J Biol Chem 279: 9043-9055.
71. Roberts JA, Evans RJ (2006). Contribution of conserved polar glutamine, asparagine and threonine residues and glycosylation to agonist action at human P2X1 receptors for ATP. J Neurochem 96: 843-852.
72. Roberts JA, Evans RJ (2007). Cysteine substitution mutants give structural insight and identify ATP binding and activation sites at P2X receptors. J Neurosci 27: 4072-4082.
73. Roberts JA, Valente M, Allsopp RC, Watt D, Evans RJ (2009). Contributions of the region Glu181 to Val200 of the extracellular loop of the human P2X1 receptor to agonist binding and gating revealed using cysteine scanning mutagenesis. J Neurochem 109: 1042-1052.
74. Roberts JA, Vial C, Digby HR, Agboh KC, Wen H, Atterbury-Thomas AE et al. (2006). Molecular properties of P2X receptors. Pflugers Arch 452: 486-500.
75. Schwarz N, Fliegert R, Adriouch S, Seman M, Guse AH, Haag F et al. (2009). Activation of the P2X7 ion channel by soluble and covalently bound ligands. Purinergic Signal 5: 139-149.
76. Silberberg SD, Swartz KJ (2009). Structural biology: trimeric ion-channel design. Nature 460: 580-581.
77. Sim JA, Broomhead HE, North RA (2008). Ectodomain lysines and suramin block of P2X1 receptors. J Biol Chem 283: 29841-29846.
78. Soto F, Garcia-Guzman M, Gomez-Hernandez JM, Hollmann M, Karschin C, Stuhmer W (1996). P2X4: an ATP-activated ionotropic receptor cloned from rat brain. Proc Natl Acad Sci U S A 93: 3684-3688.
79. Stoop R, Surprenant A, North RA (1997). Different sensitivities to pH of ATP-indiced currents at four cloned P2X receptors. J Neurophysiol 78: 1837-1840.
80. Surprenant A, Buell G, North RA (1995). P2X receptors bring new structure to ligand-gated ion channels. TINS 18: 224-229.
81. Surprenant A, North RA (2009). Signaling at purinergic P2X receptors. Annu Rev Physiol 71: 333-359.
82. Tanner NK, Cordin O, Banroques J, Doere M, Linder P (2003). The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis. Mol Cell 11: 127-138.
83. Theis K, Chen PJ, Skorvaga M, Van Houten B, Kisker C (1999). Crystal structure of UvrB, a DNA helicase adapted for nucleotide excision repair. EMBO J 18: 6899-6907.
84. Torres GE, Egan TE, Voigt MM (1998). N-linked glycosylation is essential for the functional expression of the recombinant P2X2 receptor. Biochemistry 37: 14845-14851.
85. Valera S, Hussy N, Evans RJ, Adami N, North RA, Surprenant A et al. (1994). A new class of ligand-gated ion channel defined by P2X receptor for extraxcellular ATP. Nature 371: 516-519.
86. Vulchanova L, Arvidsson U, Riedl M, Buell G, Surprenant A, North RA et al. (1996). Differential distribution of two ATP-gated ion channels (P2X receptors) determined by immunohistochemistry. Proc Natl Acad Sci U S A 93: 8063-8067.
87. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982). Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP requiring enzymes and a common nucleotide binding fold. EMBO J 1: 945-951.
88. Wilkinson WJ, Jiang LH, Surprenant A, North RA (2006). Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor. Mol Pharmacol 70: 1159-1163.
89. Yan Z, Liang Z, Tomic M, Obsil T, Stojilkovic SS (2005). Molecular determinants of the agonist binding domain of a P2X receptor channel. Mol Pharmacol 67: 1078-1088.
90. Young MT (2009). P2X receptors: dawn of the post-structure era. Trends Biochem Sci 35: 83-90.
91. Young MT, Fisher JA, Fountain SJ, Ford RC, North RA, Khakh BS (2008). Molecular shape, architecture, and size of P2X4 receptors determined using fluorescence resonance energy transfer and electron microscopy. J Biol Chem 283: 26241-26251.
92. Young MT, Pelegrin P, Surprenant A (2006). Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Mol Pharmacol 71: 92-100.
93. Zemkova H, Yan Z, Liang Z, Jelinkova I, Tomic M, Stojilkovic SS (2007). Role of aromatic and charged ectodomain residues in the P2X(4) receptor functions. J Neurochem 102: 1139-1150.