6DM1
Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction
Summary for 6DM1
| Entry DOI | 10.2210/pdb6dm1/pdb |
| EMDB information | 7961 |
| Descriptor | Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit, GLUTAMIC ACID, CYCLOTHIAZIDE, ... (4 entities in total) |
| Functional Keywords | ion channel, transport protein |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 463232.68 |
| Authors | Twomey, E.C.,Yelshanskaya, M.V.,Vassilevski, A.A.,Sobolevsky, A.I. (deposition date: 2018-06-04, release date: 2018-08-22, Last modification date: 2024-10-16) |
| Primary citation | Twomey, E.C.,Yelshanskaya, M.V.,Vassilevski, A.A.,Sobolevsky, A.I. Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors. Neuron, 99:956-968.e4, 2018 Cited by PubMed Abstract: AMPA 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. PubMed: 30122377DOI: 10.1016/j.neuron.2018.07.027 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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