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Abstract

Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To better understand how structural changes gate ion flux across the membrane, we trapped AMPA and kainate receptor subtypes in their major functional states and analyzed 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 2-fold to 4-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.

Item Type:	Article
Additional Information:	AUTHOR COPY IS AVAILABLE FREELY FROM PMC
Subjects:	Bioinformatics and Proteomics Structural Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	27 May 2016 08:12
Last Modified:	27 May 2016 08:12
URI:	http://nccs.sciencecentral.in/id/eprint/254

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