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Different gating mechanisms in glutamate receptor and K+ channels.
Sobolevsky AI, Yelshansky MV, Wollmuth LP.
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The basic structural features of channel gating in glutamate receptors (GluRs) remain unknown. Here we used covalent modification of substituted cysteines and fast agonist application to study the contribution of the M3 segment in AMPA receptor GluR-A subunits to channel structure and gating. The pattern of accessibility of substituted cysteines to extracellularly applied methanethiosulfonate reagents and the rates of their modification by these reagents, measured in either the presence or absence of glutamate, indicate that M3 forms an alpha-helix that lines the pore of the channel and is involved in gating-related movements. The voltage dependence of modification rates places the tip of the M2 loop (the Q/R site) close to the middle of M3. All of these results are consistent with pore-forming domains in GluR and K+ channels having a similar structure but inverted membrane topology. Nevertheless, GluRs lack a glycine residue at a homologous structural position as the gating hinge glycine in K+ channels. Moreover, simultaneous substitution of the only two glycines in M3 of GluR-A with alanines produced channels with gating properties indistinguishable from wild type. Given the unique role of glycines in the flexibility ofalpha-helices, our results indicate that the M3 segment in GluR does not contain a glycine gating hinge and suggest that, in contrast to the homologous domain in K+ channels, M3 is rigid during gating. The different positioning and functional significance of glycines in a key structural domain may represent the basis for the distinct features of gating in GluR and K+ channels.
Armstrong,
Structure of a glutamate-receptor ligand-binding core in complex with kainate.
1998, Pubmed
Armstrong,
Structure of a glutamate-receptor ligand-binding core in complex with kainate.
1998,
Pubmed Armstrong,
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
2000,
Pubmed Bähring,
An analysis of philanthotoxin block for recombinant rat GluR6(Q) glutamate receptor channels.
1998,
Pubmed Beck,
NMDAR channel segments forming the extracellular vestibule inferred from the accessibility of substituted cysteines.
1999,
Pubmed
,
Xenbase Bruening-Wright,
Localization of the activation gate for small conductance Ca2+-activated K+ channels.
2002,
Pubmed Burnashev,
Dimensions and ion selectivity of recombinant AMPA and kainate receptor channels and their dependence on Q/R site residues.
1996,
Pubmed Chen,
Functional characterization of a potassium-selective prokaryotic glutamate receptor.
1999,
Pubmed
,
Xenbase del Camino,
Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel.
2001,
Pubmed Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed Eilers,
Comparison of helix interactions in membrane and soluble alpha-bundle proteins.
2002,
Pubmed Flynn,
Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels.
2001,
Pubmed
,
Xenbase Javadpour,
Helix packing in polytopic membrane proteins: role of glycine in transmembrane helix association.
1999,
Pubmed Jiang,
The principle of gating charge movement in a voltage-dependent K+ channel.
2003,
Pubmed Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed Jones,
The NMDA receptor M3 segment is a conserved transduction element coupling ligand binding to channel opening.
2002,
Pubmed
,
Xenbase Karlin,
Substituted-cysteine accessibility method.
1998,
Pubmed Kohda,
Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties.
2000,
Pubmed Kuner,
A common architecture for K+ channels and ionotropic glutamate receptors?
2003,
Pubmed Kuner,
Channel-lining residues of the AMPA receptor M2 segment: structural environment of the Q/R site and identification of the selectivity filter.
2001,
Pubmed
,
Xenbase Kuner,
Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines.
1996,
Pubmed
,
Xenbase Liu,
Gated access to the pore of a voltage-dependent K+ channel.
1997,
Pubmed Mayer,
Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state.
2001,
Pubmed Panchenko,
Structural similarities between glutamate receptor channels and K(+) channels examined by scanning mutagenesis.
2001,
Pubmed
,
Xenbase Robert,
Subunit interactions and AMPA receptor desensitization.
2001,
Pubmed Rosenmund,
The tetrameric structure of a glutamate receptor channel.
1998,
Pubmed Ruiz,
Single cyclic nucleotide-gated channels locked in different ligand-bound states.
1997,
Pubmed
,
Xenbase Schorge,
Studies of NMDA receptor function and stoichiometry with truncated and tandem subunits.
2003,
Pubmed Smith,
Concentration-dependent substate behavior of native AMPA receptors.
2000,
Pubmed Sobolevsky,
Staggering of subunits in NMDAR channels.
2002,
Pubmed
,
Xenbase Sobolevsky,
Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating.
2002,
Pubmed
,
Xenbase Stern-Bach,
A point mutation in the glutamate binding site blocks desensitization of AMPA receptors.
1998,
Pubmed Sun,
Mechanism of glutamate receptor desensitization.
2002,
Pubmed Sun,
Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating.
1996,
Pubmed Wo,
Unraveling the modular design of glutamate-gated ion channels.
1995,
Pubmed Wollmuth,
Differential contribution of the NR1- and NR2A-subunits to the selectivity filter of recombinant NMDA receptor channels.
1996,
Pubmed
,
Xenbase Wood,
Structural conservation of ion conduction pathways in K channels and glutamate receptors.
1995,
Pubmed
,
Xenbase Yifrach,
Energetics of pore opening in a voltage-gated K(+) channel.
2002,
Pubmed
,
Xenbase Zhou,
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
2001,
Pubmed Zuo,
Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene.
1997,
Pubmed
,
Xenbase
