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| | <StructureSection load='3gsl' size='340' side='right'caption='[[3gsl]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='3gsl' size='340' side='right'caption='[[3gsl]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gsl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GSL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gsl]] is a 2 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=3GSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GSL FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2i1n|2i1n]], [[2fe5|2fe5]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dlg4, Dlgh4, PSD-95, Psd95 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3gsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gsl OCA], [https://pdbe.org/3gsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gsl RCSB], [https://www.ebi.ac.uk/pdbsum/3gsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gsl ProSAT]</span></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=3gsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gsl OCA], [https://pdbe.org/3gsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gsl RCSB], [https://www.ebi.ac.uk/pdbsum/3gsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gsl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DLG4_RAT DLG4_RAT]] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.<ref>PMID:15317815</ref> <ref>PMID:15358863</ref>
| + | [https://www.uniprot.org/uniprot/DLG4_RAT DLG4_RAT] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.<ref>PMID:15317815</ref> <ref>PMID:15358863</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Imperiali, B]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Olivier, N B]] | + | [[Category: Imperiali B]] |
| - | [[Category: Sainlos, M]] | + | [[Category: Olivier NB]] |
| - | [[Category: Cell junction]] | + | [[Category: Sainlos M]] |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Dlg4]]
| + | |
| - | [[Category: Glur6]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Postsynaptic cell membrane]]
| + | |
| - | [[Category: Psd-95]]
| + | |
| - | [[Category: Sap-90]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Tandem]]
| + | |
| Structural highlights
Function
DLG4_RAT Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes.
Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization.,Sainlos M, Tigaret C, Poujol C, Olivier NB, Bard L, Breillat C, Thiolon K, Choquet D, Imperiali B Nat Chem Biol. 2011 Feb;7(2):81-91. Epub 2010 Dec 26. PMID:21186349[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200
- ↑ Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101
- ↑ Sainlos M, Tigaret C, Poujol C, Olivier NB, Bard L, Breillat C, Thiolon K, Choquet D, Imperiali B. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nat Chem Biol. 2011 Feb;7(2):81-91. Epub 2010 Dec 26. PMID:21186349 doi:10.1038/nchembio.498
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