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• W4317780723 endingPage "167970" @default.
• W4317780723 startingPage "167970" @default.
• W4317780723 abstract "Ionotropic glutamate receptors are ligand-gated cation channels that play essential roles in the excitatory synaptic transmission throughout the central nervous system. A number of open-pore structures of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid (AMPA)-type glutamate receptors became available recently by cryo-electron microscopy (cryo-EM). These structures provide valuable insights into the conformation of the selectivity filter (SF), the part of the ion channel that determines the ion selectivity. Nonetheless, due to the moderate resolution of the cryo-EM structures, detailed information such as ion occupancy of monovalent and divalent cations as well as positioning of the side-chains in the SF is still missing. Here, in an attempt to obtain high-resolution information about glutamate receptor SFs, we incorporated partial SF sequences of the AMPA and kainate receptors into the bacterial tetrameric cation channel NaK, which served as a structural scaffold. We determined a series of X-ray structures of NaK-CDI, NaK-SDI and NaK-SELM mutants at 1.42-2.10 Å resolution, showing distinct ion occupation of different monovalent cations. Molecular dynamics (MD) simulations of NaK-CDI indicated the channel to be conductive to monovalent cations, which agrees well with our electrophysiology recordings. Moreover, previously unobserved structural asymmetry of the SF was revealed by the X-ray structures and MD simulations, implying its importance in ion non-selectivity of tetrameric cation channels." @default.
• W4317780723 created "2023-01-24" @default.
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• W4317780723 date "2023-03-01" @default.
• W4317780723 modified "2023-10-04" @default.
• W4317780723 title "Asymmetry and Ion Selectivity Properties of Bacterial Channel NaK Mutants Derived from Ionotropic Glutamate Receptors" @default.
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• W4317780723 doi "https://doi.org/10.1016/j.jmb.2023.167970" @default.
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• W4317780723 hasPublicationYear "2023" @default.
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