Structural mechanism of glutamate receptor activation and desensitization.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Meyerson, JR; Kumar, J; Chittori, S; Rao, P; Pierson, J; Bartesaghi, A; Mayer, ML; Subramaniam, S
Published Date
- October 2014
Published In
Volume / Issue
- 514 / 7522
Start / End Page
- 328 - 334
PubMed ID
- 25119039
Pubmed Central ID
- 25119039
Electronic International Standard Serial Number (EISSN)
- 1476-4687
International Standard Serial Number (ISSN)
- 0028-0836
Digital Object Identifier (DOI)
- 10.1038/nature13603
Language
- eng