Molecular Mechanism for the Dual Alcohol Modulation of Cys-loop Receptors

PLoS Computational Biology

Volumn 8, Issue 10, 2012, Pages

  Murail, Samuel ^a   Howard, Rebecca J ^b   Broemstrup, Torben ^a   Bertaccini, Edward J ^c,d   Harris, R Adron ^b   Trudell, James R ^d   Lindahl, Erik ^a  

^a STOCKHOLM UNIVERSITY   (Sweden)

^b UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^c VA PALO ALTO HEALTH CARE SYSTEM   (United States)

^d STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; LIGANDS; MODULATION;

ALCOHOL MODULATION; GLYCINE RECEPTOR; LIGAND-GATED ION CHANNELS; MOLECULAR MECHANISM; MOLECULAR SIMULATIONS; PROKARYOTICS; SINGLE-POINT MUTATION; TRANSMEMBRANES; WILD TYPES; Γ-AMINOBUTYRIC ACID;

ETHANOL;

EID: 84868129045     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1002710     Document Type: Article

References (55)

1. Harris RA, Trudell JR, Mihic SJ, (2008) Ethanol's molecular targets. Sci Signal 1: re7.
2. Howard RJ, Slesinger PA, Davies DL, Das J, Trudell JR, et al. (2011) Alcohol-binding sites in distinct brain proteins: the quest for atomic level resolution. Alcohol Clin Exp Res 35: 1561-1573.
3. Celentano JJ, Gibbs TT, Farb DH, (1988) Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons. Brain Res 455: 377-380.
4. Mascia MP, Machu TK, Harris RA, (1996) Enhancement of homomeric glycine receptor function by long-chain alcohols and anaesthetics. Br J Pharmacol 119: 1331-1336.
5. Nakahiro M, Arakawa O, Nishimura T, Narahashi T, (1996) Potentiation of GABA-induced Cl- current by a series of n-alcohols disappears at a cutoff point of a longer-chain n-alcohol in rat dorsal root ganglion neurons. Neurosci Lett 205: 127-130.
6. Bradley RJ, Sterz R, Peper K, (1984) The effects of alcohols and diols at the nicotinic acetylcholine receptor of the neuromuscular junction. Brain Res 295: 101-112.
7. Mihic SJ, Harris RA, (1996) Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics. J Pharmacol Exp Ther 277: 411-416.
8. Thompson AJ, Lester HA, Lummis SC, (2010) The structural basis of function in Cys-loop receptors. Q Rev Biophys 43: 449-499.
9. Baenziger JE, Corringer PJ, (2011) 3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels. Neuropharmacology 60: 116-125.
10. Borghese CM, Henderson LA, Bleck V, Trudell JR, Harris RA, (2003) Sites of excitatory and inhibitory actions of alcohols on neuronal alpha2beta4 nicotinic acetylcholine receptors. J Pharmacol Exp Ther 307: 42-52.
11. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, et al. (1997) Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 389: 385-389.
12. Hosie AM, Wilkins ME, da Silva HM, Smart TG, (2006) Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature 444: 486-489.
13. Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM, (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232: 1004-1007.
14. Unwin N, (2005) Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J Mol Biol 346: 967-989.
15. Bertaccini EJ, Trudell JR, Lindahl E, (2007) Normal-mode analysis of the glycine alpha1 receptor by three separate methods. J Chem Inf Model 47: 1572-1579.
16. Miller PS, Smart TG, (2010) Binding, activation and modulation of Cys-loop receptors. Trends Pharmacol Sci 31: 161-174.
17. Hilf RJ, Dutzler R, (2008) X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452: 375-379.
18. Bocquet N, Nury H, Baaden M, Le Poupon C, Changeux JP, et al. (2009) X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457: 111-114.
19. Hilf RJ, Dutzler R, (2009) Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457: 115-118.
20. Murail S, Wallner B, Trudell JR, Bertaccini E, Lindahl E, (2011) Microsecond simulations indicate that ethanol binds between subunits and could stabilize an open-state model of a glycine receptor. Biophys J 100: 1642-1650.
21. Cheng MH, Coalson RD, Cascio M, (2008) Molecular dynamics simulations of ethanol binding to the transmembrane domain of the glycine receptor: implications for the channel potentiation mechanism. Proteins 71: 972-981.
22. Hibbs RE, Gouaux E, (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474: 54-60.
23. Nury H, Van Renterghem C, Weng Y, Tran A, Baaden M, et al. (2011) X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469: 428-431.
24. Weng Y, Yang L, Corringer PJ, Sonner JM, (2010) Anesthetic sensitivity of the Gloeobacter violaceus proton-gated ion channel. Anesth Analg 110: 59-63.
25. Howard RJ, Murail S, Ondricek KE, Corringer PJ, Lindahl E, et al. (2011) Structural basis for alcohol modulation of a pentameric ligand-gated ion channel. Proc Natl Acad Sci U S A 108: 12149-12154.
26. Brannigan G, LeBard DN, Henin J, Eckenhoff RG, Klein ML, (2010) Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain. Proc Natl Acad Sci U S A 107: 14122-14127.
27. Lebard DN, Henin J, Eckenhoff RG, Klein ML, Brannigan G, (2012) General Anesthetics Predicted to Block the GLIC Pore with Micromolar Affinity. PLoS Comput Biol 8: e1002532.
28. Bocquet N, Prado de Carvalho L, Cartaud J, Neyton J, Le Poupon C, et al. (2007) A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature 445: 116-119.
29. Nury H, Poitevin F, Van Renterghem C, Changeux JP, Corringer PJ, et al. (2010) One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue. Proc Natl Acad Sci U S A 107: 6275-6280.
30. Fritsch S, Ivanov I, Wang H, Cheng X, (2011) Ion selectivity mechanism in a bacterial pentameric ligand-gated ion channel. Biophys J 100: 390-398.
31. Cheng MH, Coalson RD, Tang P, (2010) Molecular dynamics and brownian dynamics investigation of ion permeation and anesthetic halothane effects on a proton-gated ion channel. J Am Chem Soc 132: 16442-16449.
32. Prevost MS, Sauguet L, Nury H, Van Renterghem C, Huon C, et al. (2012) A locally closed conformation of a bacterial pentameric proton-gated ion channel. Nat Struct Mol Biol 19: 642-649.
33. Parikh RB, Bali M, Akabas MH, (2011) Structure of the M2 transmembrane segment of GLIC, a prokaryotic Cys loop receptor homologue from Gloeobacter violaceus, probed by substituted cysteine accessibility. J Biol Chem 286: 14098-14109.
34. Gonzalez-Gutierrez G, Grosman C, (2010) Bridging the gap between structural models of nicotinic receptor superfamily ion channels and their corresponding functional states. J Mol Biol 403: 693-705.
35. Gonzalez-Gutierrez G, Lukk T, Agarwal V, Papke D, Nair SK, et al. (2012) Mutations that stabilize the open state of the Erwinia chrisanthemi ligand-gated ion channel fail to change the conformation of the pore domain in crystals. Proc Natl Acad Sci USA 109: 6331-6336.
36. Bartos M, Corradi J, Bouzat C, (2009) Structural basis of activation of cys-loop receptors: the extracellular-transmembrane interface as a coupling region. Mol Neurobiol 40: 236-252.
37. Perkins DI, Trudell JR, Crawford DK, Alkana RL, Davies DL, (2010) Molecular targets and mechanisms for ethanol action in glycine receptors. Pharmacol Ther 127: 53-65.
38. Colquhoun D, (1998) Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol 125: 924-947.
39. Willenbring D, Liu LT, Mowrey D, Xu Y, Tang P, (2011) Isoflurane alters the structure and dynamics of GLIC. Biophys J 101: 1905-1912.
40. Koltchine VV, Finn SE, Jenkins A, Nikolaeva N, Lin A, et al. (1999) Agonist gating and isoflurane potentiation in the human gamma-aminobutyric acid type A receptor determined by the volume of a second transmembrane domain residue. Mol Pharmacol 56: 1087-1093.
41. Crawford DK, Trudell JR, Bertaccini EJ, Li K, Davies DL, et al. (2007) Evidence that ethanol acts on a target in Loop 2 of the extracellular domain of alpha1 glycine receptors. J Neurochem 102: 2097-2109.
42. Shen Y, Lindemeyer AK, Gonzalez C, Shao XM, Spigelman I, et al. (2012) Dihydromyricetin as a novel anti-alcohol intoxication medication. J Neurosci 32: 390-401.
43. Yevenes GE, Moraga-Cid G, Romo X, Aguayo LG, (2011) Activated G protein alpha s subunits increase the ethanol sensitivity of human glycine receptors. J Pharmacol Exp Ther 339: 386-393.
44. Nirthanan S, Garcia G 3rd, Chiara DC, Husain SS, Cohen JB, (2008) Identification of binding sites in the nicotinic acetylcholine receptor for TDBzl-etomidate, a photoreactive positive allosteric effector. J Biol Chem 283: 22051-22062.
45. Chiara DC, Dangott LJ, Eckenhoff RG, Cohen JB, (2003) Identification of nicotinic acetylcholine receptor amino acids photolabeled by the volatile anesthetic halothane. Biochemistry (Mosc) 42: 13457-13467.
46. Garcia G 3rd, Chiara DC, Nirthanan S, Hamouda AK, Stewart DS, et al. (2007) [3H]Benzophenone photolabeling identifies state-dependent changes in nicotinic acetylcholine receptor structure. Biochemistry (Mosc) 46: 10296-10307.
47. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, et al. (2005) GROMACS: fast, flexible, and free. J Comput Chem 26: 1701-1718.
48. Canutescu AA, Shelenkov AA, Dunbrack RL Jr, (2003) A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci 12: 2001-2014.
49. Rohl CA, Strauss CE, Misura KM, Baker D, (2004) Protein structure prediction using Rosetta. Methods Enzymol 383: 66-93.
50. Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, et al. (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24: 1999-2012.
51. Jorgensen W, Chandrasekhar J, Madura J, Impey R, Klein M, (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79: 926-935.
52. Berger O, Edholm O, Jahnig F, (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72: 2002-2013.
53. Humphrey W, Dalke A, Schulten K, (1996) VMD: visual molecular dynamics. J Mol Graph 14: 33-38, 27-38.
54. Le Guilloux V, Schmidtke P, Tuffery P, (2009) Fpocket: an open source platform for ligand pocket detection. BMC Bioinformatics 10: 168.
55. Smart OS, Neduvelil JG, Wang X, Wallace BA, Sansom MS, (1996) HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J Mol Graph 14: 354-360, 376.