3G3I

Crystal structure of the GluR6 ligand binding domain dimer I442H K494E I749L Q753K mutant with glutamate and NaCl at 1.37 Angstrom resolution

Summary for 3G3I

• Entry DOI: 10.2210/pdb3g3i/pdb
• Related: 3G3F 3G3G 3G3H 3G3J 3G3K
• Descriptor: Glutamate receptor, ionotropic kainate 2, GLUTAMIC ACID, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: membrane protein, cell junction, cell membrane, glycoprotein, ion transport, ionic channel, membrane, postsynaptic cell membrane, receptor, rna editing, synapse, transmembrane, transport
• Biological source: Rattus norvegicus; More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P42260
• Total number of polymer chains: 2
• Total formula weight: 59193.90

Authors

Chaudhry, C.,Mayer, M.L. (deposition date: 2009-02-02, release date: 2009-06-02, Last modification date: 2021-10-20)

Primary citation

Chaudhry, C.,Weston, M.C.,Schuck, P.,Rosenmund, C.,Mayer, M.L.
Stability of ligand-binding domain dimer assembly controls kainate receptor desensitization.
Embo J., 28:1518-1530, 2009

PubMed Abstract: AMPA and kainate receptors mediate fast synaptic transmission. AMPA receptor ligand-binding domains form dimers, which are key functional units controlling ion-channel activation and desensitization. Dimer stability is inversely related to the rate and extent of desensitization. Kainate and AMPA receptors share common structural elements, but functional measurements suggest that subunit assembly and gating differs between these subtypes. To investigate this, we constructed a library of GluR6 kainate receptor mutants and directly measured changes in kainate receptor dimer stability by analytical ultracentrifugation, which, combined with electrophysiological experiments, revealed an inverse correlation between dimer stability and the rate of desensitization. We solved crystal structures for a series of five GluR6 mutants, to understand the molecular mechanisms for dimer stabilization. We demonstrate that the desensitized state of kainate receptors acts as a deep energy well offsetting the stabilizing effects of dimer interface mutants, and that the deactivation of kainate receptor responses is dominated by entry into desensitized states. Our results show how neurotransmitter receptors with similar structures and gating mechanisms can exhibit strikingly different functional properties.

PubMed: 19339989
DOI: 10.1038/emboj.2009.86

Experimental method

X-RAY DIFFRACTION (1.371 Å)