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Structural Studies on Glutamate Receptor Gating
Author(s) -
Mayer Mark,
Meyerson Joel,
Chittori Sagar,
Subramaniam Sriram
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.95.3
Subject(s) - allosteric regulation , gating , ampa receptor , ion channel , chemistry , kainate receptor , biophysics , receptor , glutamate receptor , biochemistry , biology
A combination of structural, biophysical and functional assays, pursued over a 30 year period of research, has culminated in a gating mechanism for glutamate receptor ion channels. They key advance which led to mechanistic insight was the use of single particle cryo‐EM techniques to study the structure of individual receptor assemblies trapped in well defined conformations using appropriate combinations of high affinity ligands. At the current time we understand the broad principles, and large scale domain movements, underlying activation, desensitization, and allosteric modulation for AMPA and kainate receptors. Due to the availability of crystal structures at resolutions as high as 1.3 Å, the chemistry of ligand selectivity and in some cases the mechanism of allosteric regulation by drugs and modulatory anions and cations is understood in great detail. By contrast, the details of ion permeation remain poorly understood, due to the low resolution of ion channel domains in the receptor assembly.