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6o9g
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(New page: ==Open state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction== <StructureSection load='6o9g' size='340' side='right'caption='6o9g, [[Resolution|res...)
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Revision as of 07:37, 20 March 2019
proteopedia linkproteopedia linkOpen state GluA2 in complex with STZ and blocked by AgTx-636, after micelle signal subtraction
Structural highlights
Function[GRIA2_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Publication Abstract from PubMedAMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors. Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors.,Twomey EC, Yelshanskaya MV, Vassilevski AA, Sobolevsky AI Neuron. 2018 Aug 9. pii: S0896-6273(18)30625-1. doi:, 10.1016/j.neuron.2018.07.027. PMID:30122377[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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