2I0B

Crystal structure of the GluR6 ligand binding core ELKQ mutant dimer at 1.96 Angstroms Resolution

Summary for 2I0B

• Entry DOI: 10.2210/pdb2i0b/pdb
• Related: 1LB8 1YAE 2F36
• Descriptor: Glutamate receptor, ionotropic kainate 2, GLUTAMIC ACID, SULFATE ION, ... (4 entities in total)
• Functional Keywords: membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P42260
• Total number of polymer chains: 3
• Total formula weight: 88652.35

Authors

Mayer, M.L. (deposition date: 2006-08-10, release date: 2006-11-21, Last modification date: 2024-11-20)

Primary citation

Weston, M.C.,Schuck, P.,Ghosal, A.,Rosenmund, C.,Mayer, M.L.
Conformational restriction blocks glutamate receptor desensitization.
Nat.Struct.Mol.Biol., 13:1120-1127, 2006

PubMed Abstract: Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not by engineering the dimer interface. Crystallographic analysis of the GluR6 Y490C L752C dimer revealed relaxation from the active conformation, which functional studies reveal is not sufficient to trigger desensitization. The equivalent non-desensitizing cross-linked GluR2 mutant retained weak sensitivity to a positive allosteric modulator, which had no effect on GluR2 L483Y. These results establish that the active conformation of AMPA and kainate receptors is conserved and further show that their desensitization requires dimer rearrangements, that subtle structural differences account for their diverse functional properties and that the ligand-binding core dimer is a powerful regulator of ion-channel activity.

PubMed: 17115050
DOI: 10.1038/nsmb1178

Experimental method

X-RAY DIFFRACTION (1.96 Å)