EMD-12804

Single-particle
3.5 Å
EMD-12804 Deposition: 26/04/2021
Map released: 09/06/2021
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-12804

Resting state GluA1/A2 heterotetramer in complex with auxiliary subunit TARP gamma 8 (LBD-TMD)

EMD-12804

Single-particle
3.5 Å
EMD-12804 Deposition: 26/04/2021
Map released: 09/06/2021
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Rattus norvegicus
Sample: GluA1/A2 heterotetramer in complex with auxiliary subunit TARP gamma 8
Fitted models: 7ocd (Avg. Q-score: 0.495)

Deposition Authors: Zhang D, Watson JF , Matthews PM , Cais O, Greger IH
Gating and modulation of a hetero-octameric AMPA glutamate receptor.
Zhang D, Watson JF , Matthews PM , Cais O, Greger IH
(2021) Nature , 594 , 454 - 458
PUBMED: 34079129
DOI: doi:10.1038/s41586-021-03613-0
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1-GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.