5FTI

Crystal structure of the GluA2 K738M-T744K LBD in complex with glutamate (lithium form)

Summary for 5FTI

• Entry DOI: 10.2210/pdb5fti/pdb
• Related: 5FTH
• Descriptor: GLUTAMATE RECEPTOR 2, GLUTAMIC ACID, LITHIUM ION, ... (6 entities in total)
• Functional Keywords: signaling protein
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 2
• Total formula weight: 65404.76

Authors

Nayeem, N.,Green, T. (deposition date: 2016-01-13, release date: 2016-02-03, Last modification date: 2024-01-10)

Primary citation

Dawe, G.B.,Musgaard, M.,Aurousseau, M.R.P.,Nayeem, N.,Green, T.,Biggin, P.C.,Bowie, D.
Distinct Structural Pathways Coordinate the Activation of Ampa Receptor-Auxiliary Subunit Complexes.
Neuron, 89:1264-, 2016

PubMed 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.

PubMed: 26924438
DOI: 10.1016/J.NEURON.2016.01.038

Experimental method

X-RAY DIFFRACTION (1.35 Å)