X-ray structure of the mouse serotonin 5-HT3 receptor

Nature

Volumn 512, Issue 7514, 2014, Pages 276-281

  Hassaine, Ghérici ^a,h   Deluz, Cédric ^a   Grasso, Luigino ^a   Wyss, Romain ^a   Tol, Menno B ^a   Hovius, Ruud ^a   Graff, Alexandra ^b   Stahlberg, Henning ^b   Tomizaki, Takashi ^c   Desmyter, Aline ^d   Moreau, Christophe ^e,f   Li, Xiao Dan ^c   Poitevin, Frédéric ^g   Vogel, Horst ^a   Nury, Hugues ^a,e,f  

^a EPFL   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

^c PAUL SCHERRER INSTITUTE   (Switzerland)

^d AIX MARSEILLE UNIVERSITY   (France)

^e INSTITUT DE BIOLOGIE STRUCTURALE   (France)

^f CEA GRENOBLE   (France)

^g CNRS   (France)

^h Theranyx   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE LOOP LIGAND GATED ION CHANNEL RECEPTOR; NANOBODY; NEUROTRANSMITTER; SEROTONIN 3 RECEPTOR;

ANATOMY; MEMBRANE; NERVOUS SYSTEM; RODENT; X-RAY;

ARTICLE; BINDING SITE; CELL MEMBRANE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; HUMAN; HUMAN CELL; ION TRANSPORT; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN QUATERNARY STRUCTURE; PROTEIN STRUCTURE; VESTIBULE; X RAY;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; MICE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NEUROTRANSMITTER AGENTS; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, TERTIARY; PROTEIN SUBUNITS; RECEPTORS, SEROTONIN, 5-HT3;

EID: 84906545550     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13552     Document Type: Article

References (75)

1. Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M. & Julius, D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254, 432-437 (1991).
2. Lummis, S. C. R. 5-HT3 receptors. J. Biol. Chem. 287, 40239-40245 (2012).
3. Thompson, A. J., Lester, H. A. & Lummis, S. C. R. The structural basis of function in Cys-loop receptors. Q. Rev. Biophys. 43, 449-499 (2010).
4. Corringer, P.-J. et al. Structure and pharmacology of pentameric receptor channels: from bacteria to brain. Structure 20, 941-956 (2012).
5. Walstab, J., Rappold, G. & Niesler, B. 5-HT3 receptors: role in disease and target of drugs. Pharmacol. Ther. 128, 146-169 (2010).
6. Changeux, J.-P. 50 years of allosteric interactions: the twists and turns of the models. Nature Rev. Mol. Cell Biol. 14, 819-829 (2013).
7. Schmauder, R., Kosanic, D., Hovius, R. & Vogel, H. Correlated optical and electrical single-molecule measurements reveal conformational diffusion from ligand binding to channel gating in the nicotinic acetylcholine receptor. ChemBioChem 12, 2431-2434 (2011).
8. daCosta, C. J. B. & Baenziger, J. E. Gating of pentameric ligand-gated ion channels: structural insights and ambiguities. Structure 21, 1271-1283 (2013).
9. Auerbach, A. The gating isomerization of neuromuscular acetylcholine receptors. J. Physiol. (Lond.) 588, 573-586 (2010).
10. Unwin, N. Refined structure of the nicotinic acetylcholine receptor at 4Åresolution. J. Mol. Biol. 346, 967-989 (2005).
11. Unwin, N. & Fujiyoshi, Y. Gating movement of acetylcholine receptor caught by plunge-freezing. J. Mol. Biol. 422, 617-634 (2012).
12. Hilf, R. J. C. & Dutzler, R. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457, 115-118 (2009).
13. Bocquet, N. et al. X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 111-114 (2009).
14. Prevost, M. S. et al. A locally closed conformation of a bacterial pentameric proton-gated ion channel. Nature Struct. Mol. Biol. 19, 642-649 (2012).
15. Sauguet, L. et al. Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels. EMBO J. 32, 728-741 (2013).
16. Sauguet, L. et al. Crystal structures of a pentameric ligand-gated ion channel provide amechanismfor activation.Proc.NatlAcad. Sci.USA111, 966-971(2014).
17. Hilf, R. J. C. & Dutzler, R. X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452, 375-379 (2008).
18. Spurny, R. et al. Pentameric ligand-gated ion channel ELIC is activated by GABA andmodulated by benzodiazepines. Proc. Natl Acad. Sci. USA 109, E3028-E3034 (2012).
19. Hibbs, R. E. & Gouaux, E. Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474, 54-60 (2011).
20. Hassaïne, G. et al. Large scale expression and purification of the mouse 5-HT3 receptor. Biochim. Biophys. Acta 1828, 2544-2552 (2013).
21. Haeger, S. et al. An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors. Nature Struct. Mol. Biol. 17, 90-98 (2010).
22. Muyldermans, S. Nanobodies: natural single-domain antibodies. Annu. Rev. Biochem. 82, 775-797 (2013).
23. Livesey, M. R., Cooper, M. A., Lambert, J. J. & Peters, J. A. Rings of charge within the extracellular vestibule influence ion permeation of the 5-HT3A receptor. J. Biol. Chem. 286, 16008-16017 (2011).
24. Hansen, S. B., Wang, H. L., Taylor, P. & Sine, S. M. An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance. J. Biol. Chem. 283, 36066-36070 (2008).
25. Moroni, M., Meyer, J. O., Lahmann, C. & Sivilotti, L. G. In glycine and GABAA channels, different subunits contribute asymmetrically to channel conductance via residues in the extracellular domain. J. Biol. Chem. 286, 13414-13422 (2011).
26. Reeves, D. C., Goren, E. N., Akabas, M. H. & Lummis, S. C. Structural and electrostatic properties of the 5-HT3 receptor pore revealed by substituted cysteine accessibility mutagenesis. J. Biol. Chem. 276, 42035-42042 (2001).
27. Panicker, S., Cruz, H., Arrabit, C. & Slesinger, P. A. Evidence for a centrally located gate in the pore of a serotonin-gated ion channel. J. Neurosci. 22, 1629-1639 (2002).
28. Beckstein, O. & Sansom, M. S. P. A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor. Phys. Biol. 3, 147-159 (2006).
29. Wang, H., Cheng, X., Taylor, P., McCammon, J. & Sine, S. Control of cation permeation through the nicotinic receptor channel. PLOS Comput. Biol. 4, e41 (2008).
30. Corringer, P. J. et al. Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor. Neuron 22, 831-843 (1999).
31. Thompson, A. J. & Lummis, S. C. R. A single ring of chargedamino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor. Br. J. Pharmacol. 140, 359-365 (2003).
32. Cymes, G. D. & Grosman, C. The unanticipated complexity of the selectivity-filter glutamates of nicotinic receptors. Nature Chem. Biol. 8, 975-981 (2012).
33. Zuber, B. & Unwin, N. Structure and superorganization of acetylcholine receptorrapsyn complexes. Proc. Natl Acad. Sci. USA 110, 10622-10627 (2013).
34. Bouzat, C., Bren, N. & Sine, S. M. Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors. Neuron 13, 1395-1402 (1994).
35. Kelley, S. P., Dunlop, J. I., Kirkness, E. F., Lambert, J. J. & Peters, J. A. A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature 424, 321-324 (2003).
36. Peters, J. A. et al.Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. J. Physiol. (Lond.) 588, 587-596 (2010).
37. McKinnon, N., Bali, M. & Akabas, M. H. 5-HT3 receptor ion size selectivity is a property of the transmembrane channel, not the cytoplasmic vestibule portals. J. Gen. Physiol. 138, 453-466 (2011).
38. Carland, J. E. et al. Mutagenic analysis of the intracellular portals of the human 5-HT3A receptor. J. Biol. Chem. 288, 31592-31601 (2013).
39. Kozuska, J. L. et al. Impact of intracellular domain flexibility upon properties of activated human 5-HT3 receptors. Br. J. Pharmacol. 171, 1617-1628 (2014).
40. Brejc, K. et al. Crystal structure of an ACh-binding protein reveals the ligandbinding domain of nicotinic receptors. Nature 411, 269-276 (2001).
41. Hansen, S. B. et al. Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. EMBO J. 24, 3635-3646 (2005).
42. Kesters, D. et al. Structural basis of ligand recognition in 5-HT3 receptors. EMBO Rep. 14, 49-56 (2013).
43. Huang, S. et al. Complex between a-bungarotoxin and an a7 nicotinic receptor ligand-binding domain chimaera. Biochem. J. 454, 303-310 (2013).
44. Beene, D. L. et al. Cation-p interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 41, 10262-10269 (2002).
45. Zhong, W. et al. From ab initio quantum mechanics to molecular neurobiology: A cation-p binding site in the nicotinic receptor. Proc. Natl Acad. Sci. USA 95, 12088-12093 (1998).
46. Miles, T. F., Bower, K. S., Lester, H. A. & Dougherty, D. A. A coupled array of noncovalent interactionsimpacts the function of the 5-HT3Aserotonin receptor in an agonist-specific way. ACS Chem. Neurosci. 3, 753-760 (2012).
47. Hu, X.-Q., Zhang, L., Stewart, R. R. & Weight, F. F. Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating. J. Biol. Chem. 278, 46583-46589 (2003).
48. Lee, W. Y. & Sine, S. M. Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438, 243-247 (2005).
49. Mukhtasimova, N. & Sine, S. M. Nicotinic receptor transduction zone: invariant arginine couples to multiple electron-rich residues. Biophys. J. 104, 355-367 (2013).
50. Li, T. et al. Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging. FASEB J. 26, 3969-3979 (2012).
51. Muller, N., Girard, P., Hacker, D. L., Jordan, M. & Wurm, F. M. Orbital shaker technology for the cultivation of mammalian cells in suspension. Biotechnol. Bioeng. 89, 400-406 (2005).
52. Aimon, S. et al. Functional reconstitution of a voltage-gated potassium channel in giant unilamellar vesicles. PLoS ONE 6, e25529 (2011).
53. Montes, L.-R., Alonso, A., Goñi, F. M. & Bagatolli, L. A. Giant unilamellar vesicles electroformed from native membranes and organic lipid mixtures under physiological conditions. Biophys. J. 93, 3548-3554 (2007).
54. Hovius, R. et al. Characterization of a mouse serotonin 5-HT3 receptor purified from mammalian cells. J. Neurochem. 70, 824-834 (1998).
55. Conrath, K. et al. Camelid nanobodies raised against an integral membrane enzyme, nitric oxide reductase. Protein Sci. 18, 619-628 (2009).
56. Karlsson, R., Katsamba, P. S., Nordin, H., Pol, E. & Myszka, D. G. Analyzing a kinetic titration series using affinity biosensors. Anal. Biochem. 349, 136-147 (2006).
57. Kabsch, W. XDS. Acta Crystallogr. D 66, 125-132 (2010).
58. McCoy, A. J. Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D 63, 32-41 (2007).
59. Schröder, G. F., Levitt, M. & Brunger, A. T. Super-resolution biomolecular crystallography with low-resolution data. Nature 464, 1218-1222 (2010).
60. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486-501 (2010).
61. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213-221 (2010).
62. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352-367 (2012).
63. Blanc, E. et al. Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT. Acta Crystallogr. D 60, 2210-2221 (2004).
64. Herget, S., Ranzinger, R., Maass, K. & Lieth, C.-W. V. D. GlycoCT-a unifying sequence format for carbohydrates. Carbohydr. Res. 343, 2162-2171 (2008).
65. Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235-242 (2011).
66. The PyMOL Molecular Graphics System, Version 1.6, Schrödinger, LLC (2013).
67. Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12-21 (2010).
68. Smart, O. S., Neduvelil, J. G., Wang, X., Wallace, B. A. & Sansom, M. S. HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J. Mol. Graph. 14, 354-360 (1996).
69. Koehl, P. & Delarue, M. AQUASOL: An efficient solver for the dipolar Poisson-Boltzmann-Langevin equation. J. Chem. Phys. 132, 064101 (2010).
70. Ho, B. K. & Gruswitz, F. HOLLOW: generating accurate representations of channel and interior surfaces in molecular structures. BMC Struct. Biol. 8, 49 (2008).
71. Chovancova, E. et al. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures. PLOS Comput. Biol. 8, e1002708 (2012).
72. Calimet, N. et al. From the Cover: A gating mechanism of pentameric ligand-gated ion channels. Proc. Natl Acad. Sci. USA 110, E3987-E3996 (2013).
73. Ulens, C. et al. Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP. Proc. Natl Acad. Sci. USA 103, 3615-3620 (2006).
74. Purohit, P. & Auerbach, A. Acetylcholine receptor gating at extracellular transmembrane domain interface: the 'pre-M1' linker. J. Gen. Physiol. 130, 559-568 (2007).
75. Dang, H., England, P. M., Farivar, S. S., Dougherty, D. A. & Lester, H. A. Probing the role of a conserved M1 proline residue in 5-hydroxytryptamine3 receptor gating. Mol. Pharmacol. 57, 1114-1122 (2000).