EMDB-29371: LBD conformation 2 (LBDconf2) of GluA2 flip Q isoform of AMPA rec...

Basic information

Entry

Database: EMDB / ID: EMD-29371

• Title: LBD conformation 2 (LBDconf2) of GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma-2, with 500mM NaCl, 330uM CTZ, and 100mM glutamate (Open-Na610)
• Map data: LBDconf2, Open-Na500

Sample

• Complex: GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma-2 (KK52EE)
  • Protein or peptide: Glutamate receptor 2
• Ligand: GLUTAMIC ACID
• Ligand: CYCLOTHIAZIDE
• Ligand: water

• Keywords: ionotropic glutamate receptor / ligand gated ion channel / AMPA receptor / TARP gamma-2 / TRANSPORT PROTEIN

Function / homology

Function:

spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / AMPA glutamate receptor activity / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / asymmetric synapse / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / positive regulation of synaptic transmission / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / SNARE binding / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / protein tetramerization / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / establishment of protein localization / receptor internalization / terminal bouton / cerebral cortex development / synaptic vesicle membrane / synaptic vesicle / presynapse / presynaptic membrane / signaling receptor activity / amyloid-beta binding / growth cone / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / dendritic spine / postsynaptic density / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / endoplasmic reticulum membrane / protein kinase binding / cell surface / endoplasmic reticulum / protein-containing complex / identical protein binding / membrane / plasma membrane

Domain/homology:

Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I

Component:

Glutamate receptor 2

• Biological species: Rattus norvegicus (Norway rat)
• Method: single particle reconstruction / cryo EM / Resolution: 2.98 Å
• Authors: Nakagawa T

Funding support

United States, 1 items

Organization	Grant number	Country
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)	MH123474	United States

• Citation: Journal: Nat Struct Mol Biol / Year: 2024; Title: The open gate of the AMPA receptor forms a Ca binding site critical in regulating ion transport.; Authors: Terunaga Nakagawa / Xin-Tong Wang / Federico J Miguez-Cabello / Derek Bowie / ; Abstract: Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are cation-selective ion channels that mediate most fast excitatory neurotransmission in the brain. Although their gating mechanism has been studied extensively, understanding how cations traverse the pore has remained elusive. Here we investigated putative ion and water densities in the open pore of Ca-permeable AMPARs (rat GRIA2 flip-Q isoform) at 2.3-2.6 Å resolution. We show that the ion permeation pathway attains an extracellular Ca binding site (site-G) when the channel gate moves into the open configuration. Site-G is highly selective for Ca over Na, favoring the movement of Ca into the selectivity filter of the pore. Seizure-related N619K mutation, adjacent to site-G, promotes channel opening but attenuates Ca binding and thus diminishes Ca permeability. Our work identifies the importance of site-G, which coordinates with the Q/R site of the selectivity filter to ensure the preferential transport of Ca through the channel pore.

History

Deposition	Jan 5, 2023	-
Header (metadata) release	Mar 6, 2024	-
Map release	Mar 6, 2024	-
Update	May 1, 2024	-
Current status	May 1, 2024	Processing site: RCSB / Status: Released

Map

• File: Download / File: emd_29371.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
• Annotation: LBDconf2, Open-Na500
• Voxel size: X=Y=Z: 0.82 Å

Density

Contour Level	By AUTHOR: 0.0199
Minimum - Maximum	-0.077432856 - 0.1134879
Average (Standard dev.)	0.000041387062 (±0.0035551614)

• Symmetry: Space group: 1

Details

EMDB XML:

Map geometry	Axis order X Y Z Origin 0 0 0 Dimensions 360 360 360 Spacing 360 360 360
Cell	A=B=C: 295.2 Å α=β=γ: 90.0 °

Supplemental data

Mask #1

• File: emd_29371_msk_1.map

Half map: Half1 map, LBDconf2, Open-Na500

• File: emd_29371_half_map_1.map
• Annotation: Half1 map, LBDconf2, Open-Na500

Half map: Half2 map, LBDconf2, Open-Na500

• File: emd_29371_half_map_2.map
• Annotation: Half2 map, LBDconf2, Open-Na500