5ns9: Difference between revisions
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==Crystal structure of the GluA2 LBD (L483Y-N754S-L758V) in complex with glutamate== | ==Crystal structure of the GluA2 LBD (L483Y-N754S-L758V) in complex with glutamate== | ||
<StructureSection load='5ns9' size='340' side='right' caption='[[5ns9]], [[Resolution|resolution]] 1.44Å' scene=''> | <StructureSection load='5ns9' size='340' side='right'caption='[[5ns9]], [[Resolution|resolution]] 1.44Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ns9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NS9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NS9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ns9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NS9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NS9 FirstGlance]. <br> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ns9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ns9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | [[Category: Buffalo rat]] | ||
[[Category: Large Structures]] | |||
[[Category: Eibl, C]] | [[Category: Eibl, C]] | ||
[[Category: Plested, A J.R]] | [[Category: Plested, A J.R]] | ||
Revision as of 09:47, 16 October 2019
Crystal structure of the GluA2 LBD (L483Y-N754S-L758V) in complex with glutamateCrystal structure of the GluA2 LBD (L483Y-N754S-L758V) in complex with glutamate
Structural highlights
Function[GRIA2_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Publication Abstract from PubMedWild-type AMPA receptors display a characteristic rapidly desensitizing phenotype. Many studies point to the dimer interface between pairs of extracellular ligand binding domains as the key region controlling the rate at which the receptors desensitize. However, mutations at the extracellular end of the pore-forming regions (near the putative ion channel gate) have also been shown to alter desensitization. Here we report the behavior of single GluA4 receptors carrying one of two mutations that greatly reduce desensitization at the level of ensemble currents: the dimer interface mutation L484Y and the Lurcher mutation (A623T, GluA4-Lc) in the extracellular end of M3 (the second true transmembrane helix). Analysis of unitary currents in patches with just one active receptor showed that each mutation greatly prolongs bursts of openings without prolonging the apparent duration of individual openings. Each mutation decreases the frequency with which individual receptors visit desensitized states, but both mutant receptors still desensitize multiple times per second. Cyclothiazide (CTZ) reduced desensitization of wild-type receptors and both types of mutant receptor. Analysis of shut-time distributions revealed a form of short-lived desensitization that was resistant to CTZ and was especially prominent for GluA4-Lc receptors. Despite reducing desensitization of GluA4 L484Y receptors, CTZ decreased the amplitude of ensemble currents through GluA2 and GluA4 LY receptor mutants. Single-channel analysis and comparison of the GluA2 L483Y ligand binding domain dimer in complex with glutamate with and without CTZ is consistent with the conclusion that CTZ binding to the dimer interface prevents effects of the LY mutation to modulate receptor activation, resulting in a reduction in the prevalence of large-conductance substates that accounts for the decrease in ensemble current amplitudes. Together, the results show that similar nondesensitizing AMPA-receptor phenotypes of population currents can arise from distinct underlying molecular mechanisms that produce different types of unitary activity. Unitary Properties of AMPA Receptors with Reduced Desensitization.,Zhang W, Eibl C, Weeks AM, Riva I, Li YJ, Plested AJR, Howe JR Biophys J. 2017 Aug 29. pii: S0006-3495(17)30856-1. doi:, 10.1016/j.bpj.2017.07.030. PMID:28863863[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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