Measurement of Conformational Changes Accompanying Desensitization in an Ionotropic Glutamate Receptor
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{sup o} 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.
- Research Organization:
- Brookhaven National Laboratory (BNL) National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 930252
- Report Number(s):
- BNL--80943-2008-JA
- Journal Information:
- Cell, Journal Name: Cell Journal Issue: 1 Vol. 127; ISSN 0092-8674; ISSN CELLB5
- Country of Publication:
- United States
- Language:
- English
Similar Records
Crystal Structures of the Kainate Receptor GluR5 Ligand Binding Core Dimer with Novel GluR5-Selective Antagonists
Mechanism of Positive Allosteric Modulators Acting on AMPA Receptors