scholarly journals Structural landscape of isolated agonist-binding domains from single AMPA receptors

2011 ◽  
Vol 7 (3) ◽  
pp. 168-173 ◽  
Author(s):  
Christy F Landes ◽  
Anu Rambhadran ◽  
J Nick Taylor ◽  
Ferandre Salatan ◽  
Vasanthi Jayaraman
Keyword(s):  
Ampa Receptors ◽  
Agonist Binding ◽  
Binding Domains

scholarly journals The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors

2021 ◽  
Author(s):  
Jelena Baranovic ◽  
Sebastian Braunbeck ◽  
Nikolai Zaki ◽  
Sonja Minniberger ◽  
Miriam Chebli ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Single Channel ◽  
Basic Research ◽  
High Specificity ◽  
Direct Consequence ◽  
Binding Mode ◽  
Binding Domains

SummaryConotoxins are a large group of naturally occurring toxic peptides produced by the predatory sea snails of the genus Conus. Many of these toxins target ion channels, often with high specificity and affinity. As such, they have proven to be invaluable for basic research as well as acting as leads for therapeutic strategies. Con-ikot-ikot is the only conotoxin so far identified that targets AMPA-type glutamate receptors, the main mediators of excitatory neurotransmission in the vertebrate brain. Here, we describe how the toxin modifies the activity of AMPA receptors at the single-channel level. The toxin binds to the AMPA receptor with high affinity (EC50 = 5 nM) and once bound, takes minutes to wash out. As shown previously, it effectively blocks desensitization of AMPA receptors, however, compared to other desensitisation blockers, it is a poor stabiliser of the open channel because toxin-bound AMPA receptors undergo frequent, brief closures. We propose this is a direct consequence of its unique binding mode to the ligand binding domains. Unlike other blockers of desensitization, which stabilise individual dimers within an AMPA receptor tetramer, the toxin immobilizes all four ligand binding domains of the tetramer. This result further emphasises that quaternary reorganization of independent LBD dimers is essential for the full activity of AMPA receptors.

scholarly journals Physiological significance of high- and low-affinity agonist binding to neuronal and recombinant AMPA receptors

2008 ◽  
Vol 52 (8) ◽  
pp. 1383-1393 ◽  
Author(s):  
Markus Kessler ◽  
Erika Suzuki ◽  
Kyle Montgomery ◽  
Amy C. Arai
Keyword(s):  
Ampa Receptors ◽  
Physiological Significance ◽  
Agonist Binding

scholarly journals Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains

2016 ◽  
Vol 99 (6) ◽  
pp. 1261-1280 ◽  
Author(s):  
Sharon A. Swanger ◽  
Wenjuan Chen ◽  
Gordon Wells ◽  
Pieter B. Burger ◽  
Anel Tankovic ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Rare Variants ◽  
Agonist Binding ◽  
Binding Domains ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Noncompetitive antagonists induce cooperative AMPA receptor channel gating

2019 ◽  
Vol 151 (2) ◽  
pp. 156-173 ◽  
Author(s):  
Edward Y. Shi ◽  
Christine L. Yuan ◽  
Matthew T. Sipple ◽  
Jayasri Srinivasan ◽  
Christopher P. Ptak ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Single Channel ◽  
Channel Gating ◽  
Binding Domains ◽  
Low Concentrations ◽  
The Central Nervous System ◽  
Presynaptic Nerve Terminals ◽  
Pore Domain ◽  
Receptor Channel

Glutamate is released from presynaptic nerve terminals in the central nervous system (CNS) and spreads excitation by binding to and activating postsynaptic iGluRs. Of the potential glutamate targets, tetrameric AMPA receptors mediate fast, transient CNS signaling. Each of the four AMPA subunits in the receptor channel complex is capable of binding glutamate at its ligand-binding domains and transmitting the energy of activation to the pore domain. Homotetrameric AMPA receptor channels open in a stepwise manner, consistent with independent activation of individual subunits, and they exhibit complex kinetic behavior that manifests as temporal shifts between four different conductance levels. Here, we investigate how two AMPA receptor-selective noncompetitive antagonists, GYKI-52466 and GYKI-53655, disrupt the intrinsic step-like gating patterns of maximally activated homotetrameric GluA3 receptors using single-channel recordings from cell-attached patches. Interactions of these 2,3-benzodiazepines with residues in the boundary between the extracellular linkers and transmembrane helical domains reorganize the gating behavior of channels. Low concentrations of modulators stabilize open and closed states to different degrees and coordinate the activation of subunits so that channels open directly from closed to higher conductance levels. Using kinetic and structural models, we provide insight into how the altered gating patterns might arise from molecular contacts within the extracellular linker-channel boundary. Our results suggest that this region may be a tunable locus for AMPA receptor channel gating.

Functional high-and low affinity agonist binding sites at native dorsal horn AMPA receptors

Neuroreport ◽  
1999 ◽  
Vol 10 (8) ◽  
pp. 1803-1806 ◽  
Author(s):  
Volodymyr Rybalchenko ◽  
Rémy Schlichter
Keyword(s):  
Dorsal Horn ◽  
Ampa Receptors ◽  
Binding Sites ◽  
Agonist Binding
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