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	Proton-triggered rearrangement of the AMPA receptor N-terminal domains impacts receptor kinetics and synaptic localization.
Journal, issue, pages	Nat Struct Mol Biol, Year 2024
Publish date	Aug 13, 2024
Authors	Josip Ivica / Nejc Kejzar / Hinze Ho / Imogen Stockwell / Viktor Kuchtiak / Alexander M Scrutton / Terunaga Nakagawa / Ingo H Greger /
PubMed Abstract	AMPA glutamate receptors (AMPARs) are ion channel tetramers that mediate the majority of fast excitatory synaptic transmission. They are composed of four subunits (GluA1-GluA4); the GluA2 subunit ...AMPA glutamate receptors (AMPARs) are ion channel tetramers that mediate the majority of fast excitatory synaptic transmission. They are composed of four subunits (GluA1-GluA4); the GluA2 subunit dominates AMPAR function throughout the forebrain. Its extracellular N-terminal domain (NTD) determines receptor localization at the synapse, ensuring reliable synaptic transmission and plasticity. This synaptic anchoring function requires a compact NTD tier, stabilized by a GluA2-specific NTD interface. Here we show that low pH conditions, which accompany synaptic activity, rupture this interface. All-atom molecular dynamics simulations reveal that protonation of an interfacial histidine residue (H208) centrally contributes to NTD rearrangement. Moreover, in stark contrast to their canonical compact arrangement at neutral pH, GluA2 cryo-electron microscopy structures exhibit a wide spectrum of NTD conformations under acidic conditions. We show that the consequences of this pH-dependent conformational control are twofold: rupture of the NTD tier slows recovery from desensitized states and increases receptor mobility at mouse hippocampal synapses. Therefore, a proton-triggered NTD switch will shape both AMPAR location and kinetics, thereby impacting synaptic signal transmission.
External links	Nat Struct Mol Biol / PubMed:39138332
Methods	EM (single particle)
Resolution	2.57 - 3.69 Å
Structure data	44232 9b5z EMDB-44232, PDB-9b5z: GluA2 flip Q in complex with TARPgamma2 at pH8, consensus structure of LBD-TMD-TARPgamma2 Method: EM (single particle) / Resolution: 2.71 Å 44233 9b60 EMDB-44233, PDB-9b60: GluA2 flip Q in complex with TARPgamma2 at pH8, consensus structure of TMD-TARPgamma2 Method: EM (single particle) / Resolution: 2.57 Å 44234 9b61 EMDB-44234, PDB-9b61: GluA2 flip Q in complex with TARPgamma2 at pH5, consensus structure of LBD-TMD-TARPgamma2 Method: EM (single particle) / Resolution: 2.81 Å 44244 9b63 EMDB-44244, PDB-9b63: GluA2 flip Q in complex with TARPgamma2 at pH5, consensus structure of TMD-TARPgamma2 Method: EM (single particle) / Resolution: 2.76 Å 44245 9b64 EMDB-44245, PDB-9b64: GluA2 flip Q in complex with TARPgamma2 at pH5, class23, structure of LBD-TMD-TARPgamma2 Method: EM (single particle) / Resolution: 3.56 Å 44248 9b67 EMDB-44248, PDB-9b67: GluA2 flip Q in complex with TARPgamma2 at pH8, class1, structure of LBD-TMD-TARPgamma2 Method: EM (single particle) / Resolution: 3.39 Å 44249 9b68 EMDB-44249, PDB-9b68: GluA2 flip Q in complex with TARPgamma2 at pH8, class1, structure of NTD Method: EM (single particle) / Resolution: 3.6 Å 44250 9b69 EMDB-44250, PDB-9b69: GluA2 flip Q in complex with TARPgamma2 at pH8, class12, structure of NTD Method: EM (single particle) / Resolution: 3.69 Å 44251 9b6a EMDB-44251, PDB-9b6a: GluA2 flip Q in complex with TARPgamma2 at pH8, class12, structure of LBD-TMD-TARPgamma2 Method: EM (single particle) / Resolution: 3.35 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose
Source	mus musculus (house mouse) rattus norvegicus (Norway rat)
Keywords	TRANSPORT PROTEIN / AMPA receptor / ionotropic glutamate receptor / ion channel / auxiliary subunit