 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, June 15, 1999, 19(12):4847-4854
Mapping the Agonist Binding Site of the GABAA Receptor: Evidence for a
-Strand
Andrew J. Boileau, Amy R. Evers, Anson F. Davis, and Cynthia Czajkowski Department of Physiology, University of Wisconsin, Madison, Wisconsin 53706
GABAA receptors, along with the receptors for acetylcholine, glycine, and serotonin, are members of a ligand-gated ion channel superfamily (Ortells and Lunt, 1995). Because of the paucity of crystallographic information for these ligand-gated channels, little is known about the structure of their binding sites or how agonist binding is transduced into channel gating. We used the substituted cysteine accessibility method to obtain secondary structural information about the GABA binding site and to systematically identify residues that line its surface. Each residue from
1 Y59 to K70 was mutated to cysteine and expressed with wild-type
2 subunits in Xenopus oocytes or HEK 293 cells. The sulfhydryl-specific reagent N-biotinylaminoethyl methanethiosulfonate (MTSEA-Biotin) was used to covalently modify the cysteine-substituted residues. Receptors with cysteines substituted at positions
Key words: GABA; GABAA receptor; binding site; substituted cysteine accessibility method;
Copyright © 1999 Society for Neuroscience 0270-6474/99/19124847-08$05.00/0
This article has been cited by other articles:
J. Zhang, F. Xue, and Y. Chang
Agonist- and antagonist-induced conformational changes of loop F and their contributions to the {rho}1 GABA receptor function
J. Physiol., January 1, 2009; 587(1): 139 - 153.
[Abstract] [Full Text] [PDF]
J. Zhang, F. Xue, and Y. Chang
Structural Determinants for Antagonist Pharmacology That Distinguish the {rho}1 GABAC Receptor from GABAA Receptors
Mol. Pharmacol., October 1, 2008; 74(4): 941 - 951.
[Abstract] [Full Text] [PDF]
L. M. Sharkey and C. Czajkowski
Individually Monitoring Ligand-Induced Changes in the Structure of the GABAA Receptor at Benzodiazepine Binding Site and Non-Binding-Site Interfaces
Mol. Pharmacol., July 1, 2008; 74(1): 203 - 212.
[Abstract] [Full Text] [PDF]
S. M. Hanson and C. Czajkowski
Structural Mechanisms Underlying Benzodiazepine Modulation of the GABAA Receptor
J. Neurosci., March 26, 2008; 28(13): 3490 - 3499.
[Abstract] [Full Text] [PDF]
References
PsychiatryOnline CME, May 1, 2007; 2007(1): 2 - 2.
[Full Text]
J. H. Kloda and C. Czajkowski
Agonist-, Antagonist-, and Benzodiazepine-Induced Structural Changes in the {alpha}1 Met113-Leu132 Region of the GABAA Receptor
Mol. Pharmacol., February 1, 2007; 71(2): 483 - 493.
[Abstract] [Full Text] [PDF]
C. L. Padgett, A. P. Hanek, H. A. Lester, D. A. Dougherty, and S. C. R. Lummis
Unnatural Amino Acid Mutagenesis of the GABAA Receptor Binding Site Residues Reveals a Novel Cation-{pi} Interaction between GABA and {beta}2Tyr97
J. Neurosci., January 24, 2007; 27(4): 886 - 892.
[Abstract] [Full Text] [PDF]
T.-C. Chou
Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies
Pharmacol. Rev., September 1, 2006; 58(3): 621 - 681.
[Abstract] [Full Text] [PDF]
N. J. Harrison and S. C. R. Lummis
Locating the Carboxylate Group of GABA in the Homomeric rho GABAA Receptor Ligand-binding Pocket
J. Biol. Chem., August 25, 2006; 281(34): 24455 - 24461.
[Abstract] [Full Text] [PDF]
A. Keramidas, T. L. Kash, and N. L. Harrison
The pre-M1 segment of the {alpha}1 subunit is a transduction element in the activation of the GABAA receptor
J. Physiol., August 15, 2006; 575(1): 11 - 22.
[Abstract] [Full Text] [PDF]
G. M. C. Lema and A. Auerbach
Modes and models of GABAA receptor gating
J. Physiol., April 1, 2006; 572(1): 183 - 200.
[Abstract] [Full Text] [PDF]
J. Mercado and C. Czajkowski
Charged Residues in the {alpha}1 and beta2 Pre-M1 Regions Involved in GABAA Receptor Activation
J. Neurosci., February 15, 2006; 26(7): 2031 - 2040.
[Abstract] [Full Text] [PDF]
R. Baur and E. Sigel
Benzodiazepines Affect Channel Opening of GABAA Receptors Induced by Either Agonist Binding Site
Mol. Pharmacol., April 1, 2005; 67(4): 1005 - 1008.
[Abstract] [Full Text] [PDF]
A. Sedelnikova, C. D. Smith, S. O. Zakharkin, D. Davis, D. S. Weiss, and Y. Chang
Mapping the {rho}1 GABAC Receptor Agonist Binding Pocket: CONSTRUCTING A COMPLETE MODEL
J. Biol. Chem., January 14, 2005; 280(2): 1535 - 1542.
[Abstract] [Full Text] [PDF]
J. G. Newell, R. A. McDevitt, and C. Czajkowski
Mutation of Glutamate 155 of the GABAA Receptor {beta}2 Subunit Produces a Spontaneously Open Channel: A Trigger for Channel Activation
J. Neurosci., December 15, 2004; 24(50): 11226 - 11235.
[Abstract] [Full Text] [PDF]
I. Bohme, H. Rabe, and H. Luddens
Four Amino Acids in the {alpha} Subunits Determine the {gamma}-Aminobutyric Acid Sensitivities of GABAA Receptor Subtypes
J. Biol. Chem., August 20, 2004; 279(34): 35193 - 35200.
[Abstract] [Full Text] [PDF]
R.-Q. Huang, Z. Chen, and G. H. Dillon
Molecular Basis for Modulation of Recombinant {alpha}1{beta}2{gamma}2 GABAA Receptors by Protons
J Neurophysiol, August 1, 2004; 92(2): 883 - 894.
[Abstract] [Full Text] [PDF]
M. Mortensen, U. Kristiansen, B. Ebert, B. Frolund, P. Krogsgaard-Larsen, and T. G. Smart
Activation of single heteromeric GABAA receptor ion channels by full and partial agonists
J. Physiol., June 1, 2004; 557(2): 389 - 413.
[Abstract] [Full Text] [PDF]
D. A. Wagner, C. Czajkowski, and M. V. Jones
An Arginine Involved in GABA Binding and Unbinding But Not Gating of the GABAA Receptor
J. Neurosci., March 17, 2004; 24(11): 2733 - 2741.
[Abstract] [Full Text] [PDF]
D. Berezhnoy, Y. Nyfeler, A. Gonthier, H. Schwob, M. Goeldner, and E. Sigel
On the Benzodiazepine Binding Pocket in GABAA Receptors
J. Biol. Chem., January 30, 2004; 279(5): 3160 - 3168.
[Abstract] [Full Text] [PDF]
L. Shi and J. A. Javitch
The second extracellular loop of the dopamine D2 receptor lines the binding-site crevice
PNAS, January 13, 2004; 101(2): 440 - 445.
[Abstract] [Full Text] [PDF]
S. W. Baumann, R. Baur, and E. Sigel
Individual Properties of the Two Functional Agonist Sites in GABAA Receptors
J. Neurosci., December 3, 2003; 23(35): 11158 - 11166.
[Abstract] [Full Text] [PDF]
J. G. Newell and C. Czajkowski
The GABAA Receptor alpha 1 Subunit Pro174-Asp191 Segment Is Involved in GABA Binding and Channel Gating
J. Biol. Chem., April 4, 2003; 278(15): 13166 - 13172.
[Abstract] [Full Text] [PDF]
K. Odai, T. Sugimoto, M. Kubo, and E. Ito
Theoretical Research on Structures of {gamma}-Aminobutyric Acid and Glutamic Acid in Aqueous Conditions
J. Biochem., March 1, 2003; 133(3): 335 - 342.
[Abstract] [Full Text] [PDF]
K. Bollan, D. King, L. A. Robertson, K. Brown, P. M. Taylor, S. J. Moss, and C. N. Connolly
GABAA Receptor Composition Is Determined by Distinct Assembly Signals within alpha and beta Subunits
J. Biol. Chem., February 7, 2003; 278(7): 4747 - 4755.
[Abstract] [Full Text] [PDF]
S. W. Baumann, R. Baur, and E. Sigel
Forced Subunit Assembly in alpha 1beta 2gamma 2 GABAA Receptors. INSIGHT INTO THE ABSOLUTE ARRANGEMENT
J. Biol. Chem., November 22, 2002; 277(48): 46020 - 46025.
[Abstract] [Full Text] [PDF]
J. H. Holden and C. Czajkowski
Different Residues in the GABAA Receptor alpha 1T60-alpha 1K70 Region Mediate GABA and SR-95531 Actions
J. Biol. Chem., May 17, 2002; 277(21): 18785 - 18792.
[Abstract] [Full Text] [PDF]
J. A. Teissere and C. Czajkowski
A {beta}-Strand in the {gamma}2 Subunit Lines the Benzodiazepine Binding Site of the GABAA Receptor: Structural Rearrangements Detected during Channel Gating
J. Neurosci., July 15, 2001; 21(14): 4977 - 4986.
[Abstract] [Full Text] [PDF]
J. W. Lynch, N.-L. R. Han, J. Haddrill, K. D. Pierce, and P. R. Schofield
The Surface Accessibility of the Glycine Receptor M2-M3 Loop Is Increased in the Channel Open State
J. Neurosci., April 15, 2001; 21(8): 2589 - 2599.
[Abstract] [Full Text] [PDF]
D. A. Wagner and C. Czajkowski
Structure and Dynamics of the GABA Binding Pocket: A Narrowing Cleft that Constricts during Activation
J. Neurosci., January 1, 2001; 21(1): 67 - 74.
[Abstract] [Full Text] [PDF]
D. B. Williams and M. H. Akabas
Benzodiazepines Induce a Conformational Change in the Region of the gamma -Aminobutyric Acid Type A Receptor alpha 1-Subunit M3 Membrane-Spanning Segment
Mol. Pharmacol., November 1, 2000; 58(5): 1129 - 1136.
[Abstract] [Full Text]
J. G. Newell, M. Davies, A. N. Bateson, and S. M. J. Dunn
Tyrosine 62 of the gamma -Aminobutyric Acid Type A Receptor beta 2 Subunit Is an Important Determinant of High Affinity Agonist Binding
J. Biol. Chem., May 5, 2000; 275(19): 14198 - 14204.
[Abstract] [Full Text] [PDF]
A. M. Kucken, D. A. Wagner, P. R. Ward, J. A. Teissére, A. J. Boileau, and C. Czajkowski
Identification of Benzodiazepine Binding Site Residues in the gamma 2 Subunit of the gamma -Aminobutyric AcidA Receptor
Mol. Pharmacol., May 1, 2000; 57(5): 932 - 939.
[Abstract] [Full Text]
D. A. Sullivan and J. B. Cohen
Mapping the Agonist Binding Site of the Nicotinic Acetylcholine Receptor. ORIENTATION REQUIREMENTS FOR ACTIVATION BY COVALENT AGONIST
J. Biol. Chem., April 21, 2000; 275(17): 12651 - 12660.
[Abstract] [Full Text] [PDF]
P. M. Taylor, C. N. Connolly, J. T. Kittler, G. H. Gorrie, A. Hosie, T. G. Smart, and S. J. Moss
Identification of Residues within GABAA Receptor alpha Subunits That Mediate Specific Assembly with Receptor beta Subunits
J. Neurosci., February 15, 2000; 20(4): 1297 - 1306.
[Abstract] [Full Text] [PDF]
A. Spura, R. U. Riel, N. D. Freedman, S. Agrawal, C. Seto, and E. Hawrot
Biotinylation of Substituted Cysteines in the Nicotinic Acetylcholine Receptor Reveals Distinct Binding Modes for alpha -Bungarotoxin and Erabutoxin a
J. Biol. Chem., July 14, 2000; 275(29): 22452 - 22460.
[Abstract] [Full Text] [PDF]
S. M. O'Shea and N. L. Harrison
Arg-274 and Leu-277 of the gamma -Aminobutyric Acid Type A Receptor alpha 2 Subunit Define Agonist Efficacy and Potency
J. Biol. Chem., July 21, 2000; 275(30): 22764 - 22768.
[Abstract] [Full Text] [PDF]
M. Cascio, S. Shenkel, R. L. Grodzicki, F. J. Sigworth, and R. O. Fox
Functional Reconstitution and Characterization of Recombinant Human alpha 1-Glycine Receptors
J. Biol. Chem., June 8, 2001; 276(24): 20981 - 20988.
[Abstract] [Full Text] [PDF]
A. J. Boileau, J. G. Newell, and C. Czajkowski
GABAA Receptor beta 2 Tyr97 and Leu99 Line the GABA-binding Site. INSIGHTS INTO MECHANISMS OF AGONIST AND ANTAGONIST ACTIONS
J. Biol. Chem., January 18, 2002; 277(4): 2931 - 2937.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|