3KGC

Isolated ligand binding domain dimer of GluA2 ionotropic glutamate receptor in complex with glutamate, LY 404187 and ZK 200775

Summary for 3KGC

• Entry DOI: 10.2210/pdb3kgc/pdb
• Related: 3KG2
• Descriptor: Glutamate receptor 2, GLUTAMIC ACID, SULFATE ION, ... (6 entities in total)
• Functional Keywords: glutamate receptor, s1s2, agonist, antagonist, modulator, soluble domain, ligand binding, ion transport, ionic channel, postsynaptic cell membrane, receptor, synapse, membrane protein, glutamate, ly 404187, zk 200775, transport protein
• Biological source: Rattus norvegicus (rat); More
• Total number of polymer chains: 2
• Total formula weight: 59480.28

Authors

Sobolevsky, A.I.,Rosconi, M.P.,Gouaux, E. (deposition date: 2009-10-28, release date: 2009-12-15, Last modification date: 2024-10-30)

Primary citation

Sobolevsky, A.I.,Rosconi, M.P.,Gouaux, E.
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor
Nature, 462:745-755, 2009

PubMed Abstract: Ionotropic glutamate receptors mediate most excitatory neurotransmission in the central nervous system and function by opening a transmembrane ion channel upon binding of glutamate. Despite their crucial role in neurobiology, the architecture and atomic structure of an intact ionotropic glutamate receptor are unknown. Here we report the crystal structure of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive, homotetrameric, rat GluA2 receptor at 3.6 A resolution in complex with a competitive antagonist. The receptor harbours an overall axis of two-fold symmetry with the extracellular domains organized as pairs of local dimers and with the ion channel domain exhibiting four-fold symmetry. A symmetry mismatch between the extracellular and ion channel domains is mediated by two pairs of conformationally distinct subunits, A/C and B/D. Therefore, the stereochemical manner in which the A/C subunits are coupled to the ion channel gate is different from the B/D subunits. Guided by the GluA2 structure and site-directed cysteine mutagenesis, we suggest that GluN1 and GluN2A NMDA (N-methyl-d-aspartate) receptors have a similar architecture, with subunits arranged in a 1-2-1-2 pattern. We exploit the GluA2 structure to develop mechanisms of ion channel activation, desensitization and inhibition by non-competitive antagonists and pore blockers.

PubMed: 19946266

Experimental method

X-RAY DIFFRACTION (1.55 Å)