Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2010 May 25;10721:9891-6. doi: 10.1073/pnas.0911854107.
Show Gene links
Show Anatomy links
Role of dimer interface in activation and desensitization in AMPA receptors.
Gonzalez J, Du M, Parameshwaran K, Suppiramaniam V, Jayaraman V.
???displayArticle.abstract???
The conversion of chemical to electrical signals by the AMPA receptors is the key step by which these proteins control cognitive and motor responses. Here, we have used luminescence resonance energy transfer (LRET) to gain insight into the conformational changes induced by glutamate binding in the agonist-binding domain in functional AMPA receptors expressed in oocytes and HEK-293 cells. The LRET-based distances indicate that the interface between the upper lobes of the agonist-binding domain within a dimer is in a decoupled state in the unligated Apo state of the receptor. Agonist binding results in the formation of the dimer interface in the open-channel form of the receptor. In the continued presence of glutamate when the receptor is primarily in the desensitized state, the dimer interface is decoupled, confirming that the decoupling of the dimer interface leads to channel closure. The LRET distances also indicate that the dimer interface is preformed before activation in the L484Y mutation and also is formed in the antagonist (ZK200775)-bound form of the AMPA receptor. These results suggests that, although the preformation of the interface is not sufficient to drive channel activation, it could play a role in the energetics of activation and hence modulation of the receptor by auxiliary proteins or small molecules.
Armstrong,
Structure of a glutamate-receptor ligand-binding core in complex with kainate.
1998, Pubmed
Armstrong,
Structure of a glutamate-receptor ligand-binding core in complex with kainate.
1998,
Pubmed Armstrong,
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
2000,
Pubmed Armstrong,
Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor.
2006,
Pubmed
,
Xenbase Cha,
Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy.
1999,
Pubmed Du,
Conformational changes in the ligand-binding domain of a functional ionotropic glutamate receptor.
2005,
Pubmed Gill,
Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists.
2008,
Pubmed Gonzalez,
LRET investigations of conformational changes in the ligand binding domain of a functional AMPA receptor.
2008,
Pubmed
,
Xenbase Gouaux,
Structure and function of AMPA receptors.
2004,
Pubmed Haas,
Effect of the orientation of donor and acceptor on the probability of energy transfer involving electronic transitions of mixed polarization.
1978,
Pubmed Hogner,
Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core.
2002,
Pubmed Hollmann,
Cloned glutamate receptors.
1994,
Pubmed Jin,
Crystal structure and association behaviour of the GluR2 amino-terminal domain.
2009,
Pubmed Jin,
Mechanism of activation and selectivity in a ligand-gated ion channel: structural and functional studies of GluR2 and quisqualate.
2002,
Pubmed
,
Xenbase Jin,
Structural basis for partial agonist action at ionotropic glutamate receptors.
2003,
Pubmed
,
Xenbase Madden,
The structure and function of glutamate receptor ion channels.
2002,
Pubmed Mayer,
Glutamate receptors at atomic resolution.
2006,
Pubmed Mayer,
Glutamate receptor ion channels.
2005,
Pubmed McFeeters,
Structural mobility of the extracellular ligand-binding core of an ionotropic glutamate receptor. Analysis of NMR relaxation dynamics.
2002,
Pubmed Nakanishi,
Molecular diversity and functions of glutamate receptors.
1994,
Pubmed Oswald,
Structure of glutamate receptors.
2007,
Pubmed Plested,
AMPA receptor ligand binding domain mobility revealed by functional cross linking.
2009,
Pubmed Sobolevsky,
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor.
2009,
Pubmed Sun,
Mechanism of glutamate receptor desensitization.
2002,
Pubmed Xiao,
Quantum yields of luminescent lanthanide chelates and far-red dyes measured by resonance energy transfer.
2001,
Pubmed
