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| | ==The third PDZ domain from the synaptic protein PSD-95 (G330T mutant) in complex with a C-terminal peptide derived from CRIPT== | | ==The third PDZ domain from the synaptic protein PSD-95 (G330T mutant) in complex with a C-terminal peptide derived from CRIPT== |
| - | <StructureSection load='5hey' size='340' side='right' caption='[[5hey]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='5hey' size='340' side='right'caption='[[5hey]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hey]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HEY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hey]] 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=5HEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HEY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1be9|1be9]], [[5hdy|5hdy]], [[5heb|5heb]], [[5hed|5hed]], [[5het|5het]], [[5hf1|5hf1]], [[5hf4|5hf4]], [[5hfb|5hfb]], [[5hfc|5hfc]], [[5hfd|5hfd]], [[5hfe|5hfe]], [[5hff|5hff]]</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]] 1.5Å</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=5hey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hey OCA], [http://pdbe.org/5hey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hey RCSB], [http://www.ebi.ac.uk/pdbsum/5hey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hey 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=5hey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hey OCA], [https://pdbe.org/5hey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hey RCSB], [https://www.ebi.ac.uk/pdbsum/5hey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hey ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/CRIPT_RAT CRIPT_RAT]] Involved in the cytoskeletal anchoring of DLG4 in excitatory synapses.<ref>PMID:10570482</ref> <ref>PMID:9581762</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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5hey" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5hey" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Postsynaptic density protein 3D structures|Postsynaptic density protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Raman, A S]] | + | [[Category: Large Structures]] |
| - | [[Category: Ranganathan, R]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: White, K I]] | + | [[Category: Raman AS]] |
| - | [[Category: Adhesion]] | + | [[Category: Ranganathan R]] |
| - | [[Category: Dhr]] | + | [[Category: White KI]] |
| - | [[Category: Glgf]]
| + | |
| - | [[Category: Pdz]]
| + | |
| - | [[Category: Peptide binding protein]]
| + | |
| - | [[Category: Peptide-binding domain]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Synaptic density]]
| + | |
| 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]
Publication Abstract from PubMed
Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-binding site. These mutations provide a functional link between ligand classes and demonstrate the principle of "conditional neutrality" in mediating evolutionary adaptation. Structures show that class-bridging mutations work allosterically to open up conformational plasticity at the active site, permitting novel functions while retaining existing function. More generally, the class-bridging phenotype arises from mutations in an evolutionarily conserved network of coevolving amino acids in the PDZ family (the sector) that connects the active site to distant surface sites. These findings introduce the concept that allostery in proteins could have its origins not in protein function but in the capacity to adapt.
Origins of Allostery and Evolvability in Proteins: A Case Study.,Raman AS, White KI, Ranganathan R Cell. 2016 Jul 14;166(2):468-80. doi: 10.1016/j.cell.2016.05.047. Epub 2016 Jun, 16. PMID:27321669[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
- ↑ Raman AS, White KI, Ranganathan R. Origins of Allostery and Evolvability in Proteins: A Case Study. Cell. 2016 Jul 14;166(2):468-80. doi: 10.1016/j.cell.2016.05.047. Epub 2016 Jun, 16. PMID:27321669 doi:http://dx.doi.org/10.1016/j.cell.2016.05.047
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