Structure and function of glutamate receptor ion channels

被引:288
作者
Mayer, ML
Armstrong, N
机构
[1] NICHD, Lab Cellular & Mol Neurophysiol, NIH, DHHS, Bethesda, MD 20892 USA
[2] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA
关键词
AMPA; kainate; NMDA; crystallography; channels; structure;
D O I
10.1146/annurev.physiol.66.050802.084104
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Avast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade.
引用
收藏
页码:161 / 181
页数:27
相关论文
共 78 条
[21]   Competitive antagonism of AMPA receptors by ligands of different classes: Crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX [J].
Hogner, A ;
Greenwood, JR ;
Liljefors, T ;
Lunn, ML ;
Egebjerg, J ;
Larsen, IK ;
Gouaux, E ;
Kastrup, JS .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (02) :214-221
[22]   Structural basis for AMPA receptor activation and ligand selectivity: Crystal structures of five agonist complexes with the GluR2 ligand-binding core [J].
Hogner, A ;
Kastrup, JS ;
Jin, R ;
Liljefors, T ;
Mayer, ML ;
Egebjerg, J ;
Larsen, IK ;
Gouaux, E .
JOURNAL OF MOLECULAR BIOLOGY, 2002, 322 (01) :93-109
[23]   CLONED GLUTAMATE RECEPTORS [J].
HOLLMANN, M ;
HEINEMANN, S .
ANNUAL REVIEW OF NEUROSCIENCE, 1994, 17 :31-108
[24]   N-GLYCOSYLATION SITE TAGGING SUGGESTS A 3-TRANSMEMBRANE DOMAIN TOPOLOGY FOR THE GLUTAMATE-RECEPTOR GLUR1 [J].
HOLLMANN, M ;
MARON, C ;
HEINEMANN, S .
NEURON, 1994, 13 (06) :1331-1343
[25]   Expression and initial characterization of a soluble glycine binding domain of the N-Methyl-D-aspartate receptor NR1 subunit [J].
Ivanovic, A ;
Reiländer, H ;
Laube, B ;
Kuhse, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (32) :19933-19937
[26]   X-ray structure of a voltage-dependent K+ channel [J].
Jiang, YX ;
Lee, A ;
Chen, JY ;
Ruta, V ;
Cadene, M ;
Chait, BT ;
MacKinnon, R .
NATURE, 2003, 423 (6935) :33-41
[27]   Crystal structure and mechanism of a calcium-gated potassium channel [J].
Jiang, YX ;
Lee, A ;
Chen, JY ;
Cadene, M ;
Chait, BT ;
MacKinnon, R .
NATURE, 2002, 417 (6888) :515-522
[28]   The open pore conformation of potassium channels [J].
Jiang, YX ;
Lee, A ;
Chen, JY ;
Cadene, M ;
Chait, BT ;
MacKinnon, R .
NATURE, 2002, 417 (6888) :523-526
[29]  
JIN R, NAT NEUROSCI, V6, P803
[30]   Probing the function, conformational plasticity, and dimer-dimer contacts of the GluR2 ligand-binding core: Studies of 5-substituted willardiines and GluR2 S1S2 in the crystal [J].
Jin, RS ;
Gouaux, E .
BIOCHEMISTRY, 2003, 42 (18) :5201-5213