2I3V: Measurement Of Conformational Changes Accompanying Desensitization In An Ionotropic Glutamate Receptor: Structure Of G725c Mutant

The canonical conformational states occupied by most ligand-gated ion channels, and many cell-surface receptors, are the resting, activated, and desensitized states. While the resting and activated states of multiple receptors are well characterized, elaboration of the structural properties of the desensitized state, a state that is by definition inactive, has proven difficult. Here we use electrical, chemical, and crystallographic experiments on the AMPA-sensitive GluR2 receptor, defining the conformational rearrangements of the agonist binding cores that occur upon desensitization of this ligand-gated ion channel. These studies demonstrate that desensitization involves the rupture of an extensive interface between domain 1 of 2-fold related glutamate-binding core subunits, compensating for the ca. 21 degrees of domain closure induced by glutamate binding. The rupture of the domain 1 interface allows the ion channel to close and thereby provides a simple explanation to the long-standing question of how agonist binding is decoupled from ion channel gating upon receptor desensitization.
PDB ID: 2I3VDownload
MMDB ID: 42323
PDB Deposition Date: 2006/8/21
Updated in MMDB: 2006/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2I3V: monomeric; determined by author and by software (PISA)
Molecular Components in 2I3V
Label Count Molecule
Protein (1 molecule)
Glutamate Receptor 2(Gene symbol: Gria2)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB