4UQ6

Electron density map of GluA2em in complex with LY451646 and glutamate

Summary for 4UQ6

• Entry DOI: 10.2210/pdb4uq6/pdb
• Related: 4UQJ 4UQK 4UQQ
• EMDB information: 2684
• Descriptor: GLUTAMATE RECEPTOR 2, GLUTAMIC ACID (2 entities in total)
• Functional Keywords: transport protein, membrane protein, ion channel
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 4
• Total formula weight: 371090.83

Authors

Meyerson, J.R.,Kumar, J.,Chittori, S.,Rao, P.,Pierson, J.,Bartesaghi, A.,Mayer, M.L.,Subramaniam, S. (deposition date: 2014-06-20, release date: 2014-08-13, Last modification date: 2024-11-20)

Primary citation

Meyerson, J.R.,Kumar, J.,Chittori, S.,Rao, P.,Pierson, J.,Bartesaghi, A.,Mayer, M.L.,Subramaniam, S.
Structural Mechanism of Glutamate Receptor Activation and Desensitization
Nature, 514:328-, 2014

PubMed Abstract: Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 Å structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating.

PubMed: 25119039
DOI: 10.1038/NATURE13603

Experimental method

ELECTRON MICROSCOPY (12.8 Å)