PDBsum entry 7ocd

Membrane protein

PDB id: 7ocd

Contents

Protein chains

395 a.a.

396 a.a.

169 a.a.

Ligands

E2Q ×4

PC1 ×6

PDB id:

7ocd

Name:

Membrane protein

Title:

Resting state glua1/a2 heterotetramer in complex with auxiliary subunit tarp gamma 8 (lbd-tmd)

Structure:

Isoform flip of glutamate receptor 1. Chain: a, c. Synonym: glur-1,ampa-selective glutamate receptor 1,glur-a,glur-k1, glutamate receptor ionotropic,ampa 1,glua1. Engineered: yes. Glutamate receptor 2. Chain: d, b. Engineered: yes. Voltage-dependent calcium channel gamma-8 subunit.

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: gria1, glur1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: cacng8. Expression_system_taxid: 9606

Authors:

D.Zhang,J.F.Watson,P.M.Matthews,O.Cais,I.H.Greger

Key ref:

D.Zhang et al. (2021). Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature, 594, 454-458. PubMed id: 34079129 DOI: 10.1038/s41586-021-03613-0

Date:

26-Apr-21 Release date: 09-Jun-21

Protein chains

P19490  (GRIA1_RAT) -  Glutamate receptor 1 from Rattus norvegicus

Seq: 907 a.a.

Struc: 395 a.a.*

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 396 a.a.*

Protein chains

Q8VHW5  (CCG8_RAT) -  Voltage-dependent calcium channel gamma-8 subunit from Rattus norvegicus

Seq: 421 a.a.

Struc: 169 a.a.

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

DOI no: 10.1038/s41586-021-03613-0

Nature 594:454-458 (2021)

PubMed id: 34079129

Gating and modulation of a hetero-octameric AMPA glutamate receptor.

D.Zhang, J.F.Watson, P.M.Matthews, O.Cais, I.H.Greger.

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.