Crystal structure of a heterotetrameric NMDA receptor ion channel
Intact NMDA receptor structure revealed
For brains to develop and form memories, a signal must be transmitted from one neuron to the next. Glutamate is an important neurotransmitter that excites the receiving nerve cell by binding to an ion channel called an N-Methyl-d-Aspartate (NMDA) receptor. This activates the NMDA receptors, causing calcium ions to flood in, triggering signal transduction. Either under- or overactivation can result in a variety of neurological disorders and diseases. Karakas and Furukawa describe the crystal structure of an intact NMDA receptor composed of four separate subunits.
Science, this issue p. 992
Abstract
N-Methyl-d-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors, which mediate most excitatory synaptic transmission in mammalian brains. Calcium permeation triggered by activation of NMDA receptors is the pivotal event for initiation of neuronal plasticity. Here, we show the crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1-GluN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD regulates ion channel activity in NMDA receptors but not in non-NMDA receptors.
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Supplementary Material
Summary
Materials and Methods
Figs. S1 to S16
Table S1
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Published In
Science
Volume 344 | Issue 6187
30 May 2014
30 May 2014
Copyright
Copyright © 2014, American Association for the Advancement of Science.
Submission history
Received: 7 February 2014
Accepted: 2 May 2014
Published in print: 30 May 2014
Acknowledgments
We thank staffs at the 23-ID-B and D beamlines at the Advanced Photon System in the Argonne National Laboratory and the BL41XU beamline at the Spring 8 for their excellent beamline supports. We thank N. Simorowski for her technical support, H. Yuan and S. Traynelis for sharing unpublished data with us and for critical comments on this manuscript, and S. Harrison for making important comments on this work. This work was supported by NIH (MH085926 to H.F.), Mirus Research Award (to H.F.), and a Robertson Research Fund of Cold Spring Harbor Laboratory (to H.F.). Coordinates and structure factors have been deposited in the Protein Data Bank under accession code 4PE5. DNA constructs, recombinant virus, and proteins used in this study are available from H.F. under a material transfer agreement with Cold Spring Harbor Laboratory.
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