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| | ==High resolution structure of the GluA4 N-terminal domain (NTD)== | | ==High resolution structure of the GluA4 N-terminal domain (NTD)== |
| - | <StructureSection load='4gpa' size='340' side='right' caption='[[4gpa]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4gpa' size='340' side='right'caption='[[4gpa]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gpa]] is a 1 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=4GPA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GPA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gpa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GPA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hsy|3hsy]], [[3o21|3o21]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gpa OCA], [https://pdbe.org/4gpa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gpa RCSB], [https://www.ebi.ac.uk/pdbsum/4gpa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gpa ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur4, Gria4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gpa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gpa OCA], [http://pdbe.org/4gpa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gpa RCSB], [http://www.ebi.ac.uk/pdbsum/4gpa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gpa ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GRIA4_RAT GRIA4_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 (By similarity).<ref>PMID:12603841</ref> <ref>PMID:19102704</ref> <ref>PMID:20107073</ref> | + | [https://www.uniprot.org/uniprot/GRIA4_RAT GRIA4_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 (By similarity).<ref>PMID:12603841</ref> <ref>PMID:19102704</ref> <ref>PMID:20107073</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Ionotropic Glutamate Receptors|Ionotropic Glutamate Receptors]] | + | *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Greger, I H]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Sukumaran, M]] | + | [[Category: Greger IH]] |
| - | [[Category: Cell membrane]] | + | [[Category: Sukumaran M]] |
| - | [[Category: Ckamp44]]
| + | |
| - | [[Category: Cornichon]]
| + | |
| - | [[Category: Extracellular space]]
| + | |
| - | [[Category: Glutamate receptor]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Ion transport]]
| + | |
| - | [[Category: Ligand-gated ion channel]]
| + | |
| - | [[Category: Pbp fold]]
| + | |
| - | [[Category: Rna editing]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Tarp]]
| + | |
| - | [[Category: Transmembrane ampa receptor regulating protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
GRIA4_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 (By similarity).[1] [2] [3]
Publication Abstract from PubMed
Ionotropic glutamate receptors (iGluRs) harbor two extracellular domains: the membrane-proximal ligand-binding domain (LBD) and the distal N-terminal domain (NTD). These are involved in signal sensing: the LBD binds L-glutamate, which activates the receptor channel. Ligand binding to the NTD modulates channel function in the NMDA receptor subfamily of iGluRs, which has not been observed for the AMPAR subfamily to date. Structural data suggest that AMPAR NTDs are packed into tight dimers and have lost their signaling potential. Here, we assess NTD dynamics from both subfamilies, using a variety of computational tools. We describe the conformational motions that underly NMDAR NTD allosteric signaling. Unexpectedly, AMPAR NTDs are capable of undergoing similar dynamics; although dimerization imposes restrictions, the two subfamilies sample similar, interconvertible conformational subspaces. Finally, we solve the crystal structure of AMPAR GluA4 NTD, and combined with molecular dynamics simulations, we characterize regions pivotal for an as-yet-unexplored dynamic spectrum of AMPAR NTDs.
Comparative Dynamics of NMDA- and AMPA-Glutamate Receptor N-Terminal Domains.,Dutta A, Shrivastava IH, Sukumaran M, Greger IH, Bahar I Structure. 2012 Sep 5. PMID:22959625[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pasternack A, Coleman SK, Fethiere J, Madden DR, LeCaer JP, Rossier J, Pasternack M, Keinanen K. Characterization of the functional role of the N-glycans in the AMPA receptor ligand-binding domain. J Neurochem. 2003 Mar;84(5):1184-92. PMID:12603841
- ↑ Gill A, Birdsey-Benson A, Jones BL, Henderson LP, Madden DR. Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists. Biochemistry. 2008 Dec 30;47(52):13831-41. PMID:19102704 doi:10.1021/bi8013196
- ↑ Birdsey-Benson A, Gill A, Henderson LP, Madden DR. Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors. J Neurosci. 2010 Jan 27;30(4):1463-70. PMID:20107073 doi:30/4/1463
- ↑ Dutta A, Shrivastava IH, Sukumaran M, Greger IH, Bahar I. Comparative Dynamics of NMDA- and AMPA-Glutamate Receptor N-Terminal Domains. Structure. 2012 Sep 5. PMID:22959625 doi:http://dx.doi.org/10.1016/j.str.2012.08.012
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