7tnm

Complex GNGN2 of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM)

spinqualitylabelsall models 7tnm, resolution 4.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7tnm is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CYZ, GLU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate(1-3). An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1-O4)(4-6). Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)(6-10). Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit gamma2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity. Opening of glutamate receptor channel to subconductance levels.,Yelshanskaya MV, Patel DS, Kottke CM, Kurnikova MG, Sobolevsky AI Nature. 2022 Apr 20. pii: 10.1038/s41586-022-04637-w. doi:, 10.1038/s41586-022-04637-w. PMID:35444281 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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