Unnatural amino acid mutagenesis of the GABAA receptor binding site residues reveals a novel cation-π interaction between GABA and β2Tyr97

Journal of Neuroscience

Volumn 27, Issue 4, 2007, Pages 886-892

  Padgett, Claire L ^a   Hanek, Ariele P ^b   Lester, Henry A ^b   Dougherty, Dennis A ^b   Lummis, Sarah C R ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Cation ; Cys loop receptor; GABAA receptor binding site; Homology model; Interaction; Ligand gated ion channel; Unnatural amino acids

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; CATION; CYSTEINE; FLUORINE; PHENYLALANINE; TYROSINE;

ANIMAL CELL; ARTICLE; BINDING SITE; ELECTROPHYSIOLOGY; GENE MUTATION; HYDROGEN BOND; MUTAGENESIS; NONHUMAN; OOCYTE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INTERACTION;

AMINO ACID SUBSTITUTION; ANIMALS; BINDING SITES; CATIONS; FEMALE; GAMMA-AMINOBUTYRIC ACID; HUMANS; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; OOCYTES; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, GABA-A; TYROSINE; XENOPUS;

EID: 33846586497     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4791-06.2007     Document Type: Article

References (31)

1. A receptor structure-function studies: a reexamination in light of new acetylcholine receptor structures. Int Rev Neurobiol 62:1-43.
2. A receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital. Nature 366:565-569.
3. 3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 41:10262-10269.
4. 3 receptor revealed by unnatural amino acid mutagenesis. J Neurosci 24:9097-9104.
5. Boileau AJ, Evers AR, Davis AF, Czajkowski C (1999) Mapping the agonist binding site of the GABAA receptor: evidence for a β-strand. J Neurosci 19:4847-4854.
6. A receptor β2 Tyr97 and Leu99 line the GABA-binding site. Insights into mechanisms of agonist and antagonist actions. J Biol Chem 277:2931-2937.
7. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK (2001) Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411:269-276.
8. Cashin AL, Petersson EJ, Lester HA, Dougherty DA (2005) Using physical chemistry to differentiate nicotinic from cholinergic agonists at the nicotinic acetylcholine receptor. J Am Chem Soc 127:350-356.
9. 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.
10. A receptor structure relieved by AChBP. Trends Biochem Sci 27:280-287.
11. Dunitz JD (2004) Organic fluorine: odd man out. Chembiochem 5:614-621.
12. Forrest LR, Tang CL, Honig B (2006) On the accuracy of homology modeling and sequence alignment methods applied to membrane proteins. Biophys J 91:508-517.
13. A receptor α1T60-α1K70 region mediate GABA and SR-95531 actions. J Biol Chem 277:18785-18792.
14. Jones G, Willett P, Glen RC (1995) Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. J Mol Biol 245:43-53.
15. Kearney PC, Nowak MW, Zhong W, Silverman SK, Lester HA, Dougherty DA (1996) Dose-response relations for unnatural amino acids at the agonist binding site of the nicotinic acetylcholine receptor: tests with novel side chains and with several agonists. Mol Pharmacol 50:1401-1412.
16. Kunkel TA (1985) Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci USA 82:488-492.
17. Lee WY, Sine SM (2004) Invariant aspartic acid in muscle nicotinic receptor contributes selectively to the kinetics of agonist binding. J Gen Physiol 124:555-567.
18. + channel determined by construction of multimeric cDNAs. Neuron 9:861-871.
19. Lummis SC, L Beene D, Harrison NJ, Lester HA, Dougherty DA (2005) A cation-pi binding interaction with a tyrosine in the binding site of the GABAC receptor. Chem Biol 12:993-997.
20. Mecozzi S, West Jr AP, Dougherty DA (1996) Cation-pi interactions in aromatics of biological and medicinal interest: electrostatic potential surfaces as a useful qualitative guide. Proc Natl Acad Sci USA 93:10566-10571.
21. Mu TW, Lester HA, Dougherty DA (2003) Different binding orientations for the same agonist at homologous receptors: a lock and key or a simple wedge? J Am Chem Soc 125:6850-6851.
22. Nowak MW, Kearney PC, Sampson JR, Saks ME, Labarca CG, Silverman SK, Zhong W, Thorson J, Abelson JN, Davidson N, Schultz PG, Dougherty DA, Lester HA (1995) Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells. Science 268:439-442.
23. Nowak MW, Gallivan JP, Silverman SK, Labarca CG, Dougherty DA, Lester HA (1998) In vivo incorporation of unnatural amino acids into ion channels in Xenopus oocyte expression system. Methods Enzymol 293:504-529.
24. 3 receptor pore revealed by substituted cysteine accessibility mutagenesis. J Biol Chem 276:42035-42042.
25. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779-815.
26. Shi J, Blundell TL, Mizuguchi K (2001) FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. J Mol Biol 310:243-257.
27. A receptor channels. EMBO J 11:2017-2023.
28. 3H]muscimol photoaffinity substrate in the bovine gamma-aminobutyric acidA receptor alpha subunit. J Biol Chem 269:20380-20387.
29. 3 receptor. Mol Membr Biol 23:442-451.
30. A receptor. J Neurosci 24:2733-2741.
31. Zhong W, Gallivan JP, Zhang Y, Li L, Lester HA, Dougherty DA (1998) From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding site in the nicotinic receptor. Proc Natl Acad Sci USA 95:12088-12093.