Journal Article

PUBDB-2023-07326

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Asymmetry and Ion Selectivity Properties of Bacterial Channel NaK Mutants Derived from Ionotropic Glutamate Receptors

Minniberger, S.Extern* ; Abdolvand, S. ; Braunbeck, S. ; Sun, H. (Corresponding author) ; Plested, A. J. R. (Corresponding author)

2023
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jmb.2023.167970

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.

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Contributing Institute(s):

1. DOOR-User (DOOR ; HAS-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. DFG project 390540038 - EXC 2008: Unifying Systems in Catalysis "UniSysCat" (390540038) (390540038)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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