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 Tikhonov, D. B.
Right arrow Articles by Magazanik, L. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tikhonov, D. B.
Right arrow Articles by Magazanik, L. G.

Biophys J, October 1999, p. 1914-1926, Vol. 77, No. 4

Intersegment Hydrogen Bonds as Possible Structural Determinants of the N/Q/R Site in Glutamate Receptors

Denis B. Tikhonov, Boris S. Zhorov, and Lev G. Magazanik

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg 194223, Russia

Specific electrophysiological and pharmacological properties of ionic channels in NMDA, AMPA, and kainate subtypes of ionotropic glutamate receptors (GluRs) are determined by the Asn (N), Gln (Q), and Arg (R) residues located at homologous positions of the pore-lining M2 segments (the N/Q/R site). Presumably, the N/Q/R site is located at the apex of the reentrant membrane loop and forms the narrowest constriction of the pore. Although the shorter Asn residues are expected to protrude in the pore to a lesser extent than the longer Gln residues, the effective dimension of the NMDA channel (corresponding to the size of the largest permeant organic cation) is, surprisingly, smaller than that of the AMPA channel. To explain this paradox, we propose that the N/Q/R residues form macrocyclic structures (rings) stabilized by H-bonds between a NH2 group in the side chain of a given M2 segment and a C==O group of the main chain in the adjacent M2 segment. Using Monte Carlo minimization, we have explored conformational properties of the rings. In the Asn, but not in the Gln ring, the side-chain oxygens protruding into the pore may facilitate ion permeation and accept H-bonds from the blocking drugs. In this way, the model explains different electrophysiological and pharmacological properties of NMDA and non-NMDA GluR channels. The ring of H-bonded polar residues at the pore narrowing resembles the ring of four Thr75 residues observed in the crystallographic structure of the KcsA K+ channel.

Biophys J, October 1999, p. 1914-1926, Vol. 77, No. 4
© 1999 by the Biophysical Society   0006-3495/99/10/1914/13  $2.00


This article has been cited by other articles:


Home page
 Biophys. JHome page
D. B. Tikhonov and B. S. Zhorov
Modeling P-Loops Domain of Sodium Channel: Homology with Potassium Channels and Interaction with Ligands
Biophys. J., January 1, 2005; 88(1): 184 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
B. Vissel, J. J. Krupp, S. F. Heinemann, and G. L. Westbrook
Intracellular Domains of NR2 Alter Calcium-Dependent Inactivation of N-Methyl-D-aspartate Receptors
Mol. Pharmacol., March 1, 2002; 61(3): 595 - 605.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the Biophysical Society.