PDB-8fq6: LBD of GluA2 flip Q isoform of AMPA receptor in complex with gain...

Basic information

• Entry: Database: PDB / ID: 8fq6
• Title: LBD of GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma2, with 150mM CaCl2, 330uM CTZ, and 100mM L-glutamate (Open-Ca150)
• Components: Glutamate receptor 2
• Keywords: TRANSPORT PROTEIN / Inotropic glutamate receptors / AMPA receptors / ligand gated ion channel / auxiliary subunit / TARP / stargazin / TARP gamma2 / glutamate / calcium / neurotransmitter receptor / synaptic transmission

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:

CYCLOTHIAZIDE / GLUTAMIC ACID / Glutamate receptor 2

• Biological species: Rattus norvegicus (Norway rat)
• Method: ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.14 Å
• Authors: Nakagawa, T.

Funding support

United States, 1items

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	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Feb 28, 2024	Provider: repository / Type: Initial release
Revision 1.1	Mar 13, 2024	Group: Database references / Category: citation / citation_author Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2	May 1, 2024	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last

Assembly

Deposited unit

B: Glutamate