Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Architecture, dynamics and biogenesis of GluA3 AMPA glutamate receptors.
Journal, issue, pages	Nature, Year 2025
Publish date	Jul 1, 2025
Authors	Aditya Pokharna / Imogen Stockwell / Josip Ivica / Bishal Singh / Johannes Schwab / Carlos Vega-Gutiérrez / Beatriz Herguedas / Ondrej Cais / James M Krieger / Ingo H Greger /
PubMed Abstract	AMPA-type glutamate receptors (AMPARs) mediate the majority of excitatory neurotransmission in the brain. Assembled from combinations of four core subunits, GluA1-4 and around 20 auxiliary subunits, ...AMPA-type glutamate receptors (AMPARs) mediate the majority of excitatory neurotransmission in the brain. Assembled from combinations of four core subunits, GluA1-4 and around 20 auxiliary subunits, their molecular diversity tunes information transfer and storage in a brain-circuit-specific manner. GluA3, a subtype strongly associated with disease, functions as both a fast-transmitting Ca-permeable AMPAR at sensory synapses, and as a Ca-impermeable receptor at cortical synapses. Here we present cryo-electron microscopy structures of the Ca-permeable GluA3 homomer, which substantially diverges from other AMPARs. The GluA3 extracellular domain tiers (N-terminal domain (NTD) and ligand-binding domain (LBD)) are closely coupled throughout gating states, creating interfaces that impact signalling and contain human disease-associated mutations. Central to this architecture is a stacking interaction between two arginine residues (Arg163) in the NTD dimer interface, trapping a unique NTD dimer conformation that enables close contacts with the LBD. Rupture of the Arg163 stack not only alters the structure and dynamics of the GluA3 extracellular region, but also increases receptor trafficking and the expression of GluA3 heteromers at the synapse. We further show that a mammalian-specific GluA3 trafficking checkpoint determines the conformational stability of the LBD tier. Thus, specific design features define communication and biogenesis of GluA3, offering a framework to examine this disease-associated glutamate receptor.
External links	Nature / PubMed:40592473
Methods	EM (single particle)
Resolution	2.59 - 3.77 Å
Structure data	52325 9hpc EMDB-52325, PDB-9hpc: The TMD and the LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state. Method: EM (single particle) / Resolution: 2.59 Å 52326 9hpd EMDB-52326, PDB-9hpd: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the open state. Method: EM (single particle) / Resolution: 2.96 Å 52327 9hpe EMDB-52327: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state. PDB-9hpe: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the apo state Method: EM (single particle) / Resolution: 2.9 Å 52328 9hpf EMDB-52328, PDB-9hpf: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3- TARP gamma2 in the desensitised state. Method: EM (single particle) / Resolution: 3.77 Å 52329 9hpg EMDB-52329, PDB-9hpg: The NTD dimer and the interfacing LBD region of the AMPAR complex GluA3(R439G,R163I)- TARP gamma2 in the apo state. Method: EM (single particle) / Resolution: 3.35 Å 52332 9hpk EMDB-52332, PDB-9hpk: Open state TMD-LBD of the GluA3(R439G) with TARP gamma2 Method: EM (single particle) / Resolution: 2.59 Å 53109 9qfh EMDB-53109, PDB-9qfh: The composite map of of the AMPAR complex GluA3- TARP gamma2 in the apo state. Method: EM (single particle) / Resolution: 2.9 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER
Source	Rattus (rat) rattus norvegicus (Norway rat)
Keywords	MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission / ion channel / glutamate