Article

Glutamate receptors at atomic resolution.

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Nature (Impact Factor: 42.35). 04/2006; 440(7083):456-62. DOI: 10.1038/nature04709
Source: PubMed

ABSTRACT At synapses throughout the brain and spinal cord, the amino-acid glutamate is the major excitatory neurotransmitter. During evolution, a family of glutamate-receptor ion channels seems to have been assembled from a kit consisting of discrete ligand-binding, ion-channel, modulatory and cytoplasmic domains. Crystallographic studies that exploit this unique architecture have greatly aided structural analysis of the ligand-binding core, but the results also pose a formidable challenge, namely that of resolving the allosteric mechanisms by which individual domains communicate and function in an intact receptor.

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Available from: Mark L Mayer, Jul 08, 2015
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    • "Early evidence favored a pentameric structure for iGluRs based on the sizes of chemically cross-linked proteins and the number of distinct channel activities produced by the mixture of two subunits (Dingledine et al., 1999). However, an overwhelming number of studies analyzing structures, desensitization properties and cross-linking between subunits through cysteines now suggest that mammalian iGluRs assemble as tetramers (reviewed in Mayer, 2006; Traynelis et al., 2010). In mammals, functional ligand-gated channels can be formed from either homo-or heteromers of four subunits within the same agonist class (Rosenmund et al., 1998). "
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    • "The availability of a full length iGluR structure, combined with high resolution structures for the isolated ATD and LBDs for multiple iGluR subtypes, has given unprecedented insight into the molecular function of this important family of neurotransmitter receptors. More than one hundred high resolution structures for ligand binding domain complexes for multiple iGluR subtypes with agonists, partial agonists, competitive antagonists, and allosteric modulators of desensitization, reveal with unrivalled clarity the mechanisms underlying the subtype selective pharmacology which formed the historical basis for classification of iGluR subtypes (Mayer, 2006; Pohlsgaard et al., 2011; Stawski et al., 2010; Traynelis et al., 2010). Work is rapidly progressing on the amino terminal domains, but here key questions remained to be addressed. "
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    • "The electron microscopic picture of nicotinic acetylcholine receptors was the first to reveal the threedimensional structure of pLGIC receptors with intermediate resolution (Unwin, 1995). By now we have learned several highresolution structures of these LGIC receptor families via X-ray crystallography (Hilf and Dutzler, 2009; Mayer, 2006). All three families have pseudo-symmetric oligomeric structures (Browne et al., 2010; Changeux and Edelstein, 2005; Sobolevsky et al., 2009). "
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