 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, February 15, 2003, 23(4):1219
Amino-Acid Residues Involved in Glutamate Receptor 6 Kainate Receptor Gating and Desensitization
Mark W. Fleck, Elizabeth Cornell, and Stephanie J. Mah Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208
The glutamate receptor (GluR) agonist-binding site consists of amino acid residues in the extracellular S1 and S2 segments in the N-terminal and M3-M4 loop regions, respectively. Molecular and atomic level structural analyses have identified specific S1 and S2 residues that interact directly with ligands, interact with one another in a dimeric configuration, and influence channel gating and desensitization properties of AMPA receptors. Other studies suggest that KA receptor gating and desensitization may differ mechanistically. In particular, a leucine (L) to tyrosine (Y) mutation in the S1 segment of AMPA receptors is sufficient to block desensitization, whereas KA receptors naturally contain a tyrosine residue at the equivalent position (Y751 in GluR6) but retain the fast-desensitizing phenotype. We hypothesized that KA receptor desensitization is preserved by a compensatory substitution in the S2 segment. We generated a series of GluR6 mutants that converted individual S2 domain residues to their AMPA receptor equivalents. Various S2 mutations had effects on the kinetics of desensitization and recovery from desensitization, but no single amino acid substitution was found to block desensitization, as in the L/Y mutant AMPA receptors, or to prevent desensitization to KA. Other mutations designed to neutralize residues thought to interact across the dimer interface had dramatic effects on channel gating and desensitization. These results are consistent with a close but imperfect structural homology between AMPA and KA receptors and support the role of conserved S1S2 domain interactions at the dimer interface in GluR channel function.
Key words: glutamate receptor; binding site; desensitization; S2-segment; dimer; mutagenesis
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341219-09$05.00/0
This article has been cited by other articles:
M. B. Gill, P. Vivithanaporn, and G. T. Swanson
Glutamate Binding and Conformational Flexibility of Ligand-binding Domains Are Critical Early Determinants of Efficient Kainate Receptor Biogenesis
J. Biol. Chem., May 22, 2009; 284(21): 14503 - 14512.
[Abstract] [Full Text] [PDF]
S. Martin, T. Bouschet, E. L. Jenkins, A. Nishimune, and J. M. Henley
Bidirectional Regulation of Kainate Receptor Surface Expression in Hippocampal Neurons
J. Biol. Chem., December 26, 2008; 283(52): 36435 - 36440.
[Abstract] [Full Text] [PDF]
M. Du, A. Rambhadran, and V. Jayaraman
Luminescence Resonance Energy Transfer Investigation of Conformational Changes in the Ligand Binding Domain of a Kainate Receptor
J. Biol. Chem., October 3, 2008; 283(40): 27074 - 27078.
[Abstract] [Full Text] [PDF]
Y. Zhang, N. Nayeem, and T. Green
Mutations to the Kainate Receptor Subunit GluR6 Binding Pocket That Selectively Affect Domoate Binding
Mol. Pharmacol., October 1, 2008; 74(4): 1163 - 1169.
[Abstract] [Full Text] [PDF]
S. M. Schmid, C. Korber, S. Herrmann, M. Werner, and M. Hollmann
A Domain Linking the AMPA Receptor Agonist Binding Site to the Ion Pore Controls Gating and Causes lurcher Properties when Mutated
J. Neurosci., November 7, 2007; 27(45): 12230 - 12241.
[Abstract] [Full Text] [PDF]
P. Vivithanaporn, L. L. Lash, W. Marszalec, and G. T. Swanson
Critical Roles for the M3 S2 Transduction Linker Domain in Kainate Receptor Assembly and Postassembly Trafficking
J. Neurosci., September 26, 2007; 27(39): 10423 - 10433.
[Abstract] [Full Text] [PDF]
H. Hald, P. Naur, D. S. Pickering, D. Sprogoe, U. Madsen, D. B. Timmermann, P. K. Ahring, T. Liljefors, A. Schousboe, J. Egebjerg, et al.
Partial Agonism and Antagonism of the Ionotropic Glutamate Receptor iGLuR5: STRUCTURES OF THE LIGAND-BINDING CORE IN COMPLEX WITH DOMOIC ACID AND 2-AMINO-3-[5-tert-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL]PROPIONIC ACID
J. Biol. Chem., August 31, 2007; 282(35): 25726 - 25736.
[Abstract] [Full Text] [PDF]
Y. Zhang, N. Nayeem, M. H. Nanao, and T. Green
Interface Interactions Modulating Desensitization of the Kainate-Selective Ionotropic Glutamate Receptor Subunit GluR6
J. Neurosci., September 27, 2006; 26(39): 10033 - 10042.
[Abstract] [Full Text] [PDF]
M. W. Fleck
Glutamate Receptors and Endoplasmic Reticulum Quality Control: Looking beneath the Surface
Neuroscientist, June 1, 2006; 12(3): 232 - 244.
[Abstract] [PDF]
R. Jin, S. Clark, A. M. Weeks, J. T. Dudman, E. Gouaux, and K. M. Partin
Mechanism of Positive Allosteric Modulators Acting on AMPA Receptors
J. Neurosci., September 28, 2005; 25(39): 9027 - 9036.
[Abstract] [Full Text] [PDF]
S. J. Mah, E. Cornell, N. A. Mitchell, and M. W. Fleck
Glutamate Receptor Trafficking: Endoplasmic Reticulum Quality Control Involves Ligand Binding and Receptor Function
J. Neurosci., March 2, 2005; 25(9): 2215 - 2225.
[Abstract] [Full Text] [PDF]
L. Valluru, J. Xu, Y. Zhu, S. Yan, A. Contractor, and G. T. Swanson
Ligand Binding Is a Critical Requirement for Plasma Membrane Expression of Heteromeric Kainate Receptors
J. Biol. Chem., February 18, 2005; 280(7): 6085 - 6093.
[Abstract] [Full Text] [PDF]
M. H. Nanao, T. Green, Y. Stern-Bach, S. F. Heinemann, and S. Choe
Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid
PNAS, February 1, 2005; 102(5): 1708 - 1713.
[Abstract] [Full Text] [PDF]
J. C. Quirk, E. R. Siuda, and E. S. Nisenbaum
Molecular Determinants Responsible for Differences in Desensitization Kinetics of AMPA Receptor Splice Variants
J. Neurosci., December 15, 2004; 24(50): 11416 - 11420.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|