TY - JOUR
T1 - Structural Mechanisms of Gating in Ionotropic Glutamate Receptors
AU - Twomey, Edward C.
AU - Sobolevsky, Alexander I.
N1 - Funding Information:
*Department of Biochemistry and Molecular Biophysics, Columbia University, 650 W. 168th St., New York, NY 10032. E-mail: as4005@cumc.columbia.edu. Telephone: 212-305-4249. ORCID Edward C. Twomey: 0000-0002-1855-1586 Alexander I. Sobolevsky: 0000-0001-5181-8644 Funding E.C.T. is supported by National Institutes of Health (NIH) Grant F31 NS093838. A.I.S. is supported by NIH Grants R01 NS083660 and R01 CA206573, the Amgen Young Investigator Award, and the Irma T. Hirschl Career Scientist Award. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/1/23
Y1 - 2018/1/23
N2 - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the majority of excitatory neurotransmission in the central nervous system. iGluRs open their ion channels in response to binding of the neurotransmitter glutamate, rapidly depolarize the postsynaptic neuronal membrane, and initiate signal transduction. Recent studies using X-ray crystallography and cryo-electron microscopy have determined full-length iGluR structures that (1) uncover the receptor architecture in an unliganded, resting state, (2) reveal conformational changes produced by ligands in order to activate iGluRs, open their ion channels, and conduct ions, and (3) show how activated, glutamate-bound iGluRs can adopt a nonconducting desensitized state. These new findings, combined with the results of previous structural and functional experiments, kinetic and molecular modeling, mutagenesis, and biochemical analyses, provide new views on the structural mechanisms of iGluR gating.
AB - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the majority of excitatory neurotransmission in the central nervous system. iGluRs open their ion channels in response to binding of the neurotransmitter glutamate, rapidly depolarize the postsynaptic neuronal membrane, and initiate signal transduction. Recent studies using X-ray crystallography and cryo-electron microscopy have determined full-length iGluR structures that (1) uncover the receptor architecture in an unliganded, resting state, (2) reveal conformational changes produced by ligands in order to activate iGluRs, open their ion channels, and conduct ions, and (3) show how activated, glutamate-bound iGluRs can adopt a nonconducting desensitized state. These new findings, combined with the results of previous structural and functional experiments, kinetic and molecular modeling, mutagenesis, and biochemical analyses, provide new views on the structural mechanisms of iGluR gating.
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U2 - 10.1021/acs.biochem.7b00891
DO - 10.1021/acs.biochem.7b00891
M3 - Review article
C2 - 29037031
AN - SCOPUS:85041040131
SN - 0006-2960
VL - 57
SP - 267
EP - 276
JO - Biochemistry
JF - Biochemistry
IS - 3
ER -