help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arinaminpathy, Y.
Right arrow Articles by Biggin, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arinaminpathy, Y.
Right arrow Articles by Biggin, P. C.

Biophys J, February 2002, p. 676-683, Vol. 82, No. 2

Molecular Dynamics Simulations of the Ligand-Binding Domain of the Ionotropic Glutamate Receptor GluR2

Yalini Arinaminpathy, Mark S. P. Sansom, and Philip C. Biggin

Laboratory of Molecular Biophysics, Department of Biochemistry, The University of Oxford, Oxford OX1 3QU, United Kingdom

Ionotropic glutamate receptors are essential for fast synaptic nerve transmission. Recent x-ray structures for the ligand-binding (S1S2) region of the GluR2 alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive receptor have suggested how differences in protein/ligand interactions may determine whether a ligand will behave as a full agonist. We have used multiple molecular dynamics simulations of 2-5 ns duration to explore the structural dynamics of GluR2 S1S2 in the presence and absence of glutamate and in a complex with kainate. Our studies indicate that not only is the degree of domain closure dependent upon interactions with the ligand, but also that protein/ligand interactions influence the motion of the S2 domain with respect to S1. Differences in domain mobility between the three states (apo-S1S2, glutamate-bound, and kainate-bound) are surprisingly clear-cut. We discuss how these changes in dynamics may provide an explanation relating the mechanism of transmission of the agonist-binding event to channel opening. We also show here how the glutamate may adopt an alternative mode of binding not seen in the x-ray structure, which involves a key threonine (T480) side chain flipping into a new conformation. This new conformation results in an altered pattern of hydrogen bonding at the agonist-binding site.

Biophys J, February 2002, p. 676-683, Vol. 82, No. 2
© 2002 by the Biophysical Society   0006-3495/02/02/676/08  $2.00


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. L. Blanke and A. M. J. VanDongen
Constitutive Activation of the N-Methyl-D-aspartate Receptor via Cleft-spanning Disulfide Bonds
J. Biol. Chem., August 1, 2008; 283(31): 21519 - 21529.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. L. Blanke and A. M. J. VanDongen
The NR1 M3 Domain Mediates Allosteric Coupling in the N-Methyl-D-aspartate Receptor
Mol. Pharmacol., August 1, 2008; 74(2): 454 - 465.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Arinaminpathy, M. S. P. Sansom, and P. C. Biggin
Binding Site Flexibility: Molecular Simulation of Partial and Full Agonists within a Glutamate Receptor
Mol. Pharmacol., January 1, 2006; 69(1): 11 - 18.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. B. Hansen, R. P. Clausen, E. J. Bjerrum, C. Bechmann, J. R. Greenwood, C. Christensen, J. L. Kristensen, J. Egebjerg, and H. Brauner-Osborne
Tweaking Agonist Efficacy at N-Methyl-D-aspartate Receptors by Site-Directed Mutagenesis
Mol. Pharmacol., December 1, 2005; 68(6): 1510 - 1523.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
T. Stockner, H. J. Vogel, and D. P. Tieleman
A Salt-Bridge Motif Involved in Ligand Binding and Large-Scale Domain Motions of the Maltose-Binding Protein
Biophys. J., November 1, 2005; 89(5): 3362 - 3371.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. R. Madden, N. Armstrong, D. Svergun, J. Perez, and P. Vachette
Solution X-ray Scattering Evidence for Agonist- and Antagonist-induced Modulation of Cleft Closure in a Glutamate Receptor Ligand-binding Domain
J. Biol. Chem., June 24, 2005; 280(25): 23637 - 23642.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
J. D. Campbell, S. S. Deol, F. M. Ashcroft, I. D. Kerr, and M. S. P. Sansom
Nucleotide-Dependent Conformational Changes in HisP: Molecular Dynamics Simulations of an ABC Transporter Nucleotide-Binding Domain
Biophys. J., December 1, 2004; 87(6): 3703 - 3715.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
T. L. Kalbaugh, H. M. A. VanDongen, and A. M. J. VanDongen
Ligand-Binding Residues Integrate Affinity and Efficacy in the NMDA Receptor
Mol. Pharmacol., August 1, 2004; 66(2): 209 - 219.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
C. Domene, A. Grottesi, and M. S. P. Sansom
Filter Flexibility and Distortion in a Bacterial Inward Rectifier K+ Channel: Simulation Studies of KirBac1.1
Biophys. J., July 1, 2004; 87(1): 256 - 267.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
R. L. McFEETERS and R. E. OSWALD
Emerging structural explanations of ionotropic glutamate receptor function
FASEB J, March 1, 2004; 18(3): 428 - 438.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Biophysical Society.