PDBsum entry 5fth

Signaling protein

PDB id: 5fth

Contents

Protein chains

248 a.a.

249 a.a.

254 a.a.

Ligands

GLU ×3

Metals

_ZN ×5

PDB id:

5fth

Name:

Signaling protein

Title:

Crystal structure of the glua2 k738m-t744k lbd in complex with glutamate (zinc form)

Structure:

Glutamate receptor 2. Chain: a, b, c. Fragment: ligand binding domain, unp residues 404-527,653-796. Synonym: glur-2, ampa-selective glutamate receptor 2, glur-b, glur- k2, glutamate receptor ionotropic, ampa 2, glua2. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: rosetta-gami b.

Resolution:

2.90Å R-factor: 0.245 R-free: 0.283

Authors:

N.Nayeem,T.Green

Key ref:

G.B.Dawe et al. (2016). Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. Neuron, 89, 1264-1276. PubMed id: 26924438 DOI: 10.1016/j.neuron.2016.01.038

Date:

13-Jan-16 Release date: 03-Feb-16

Protein chain

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 248 a.a.*

Protein chain

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 249 a.a.*

Protein chain

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 254 a.a.*

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

DOI no: 10.1016/j.neuron.2016.01.038

Neuron 89:1264-1276 (2016)

PubMed id: 26924438

Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes.

G.B.Dawe, M.Musgaard, M.R.Aurousseau, N.Nayeem, T.Green, P.C.Biggin, D.Bowie.

ABSTRACT

Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits.