|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5ypo' size='340' side='right'caption='[[5ypo]], [[Resolution|resolution]] 2.29Å' scene=''> | | <StructureSection load='5ypo' size='340' side='right'caption='[[5ypo]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ypo]] is a 4 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=5YPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YPO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ypo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YPO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 2.29Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dlg4, Dlgh4, 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=5ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypo OCA], [https://pdbe.org/5ypo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ypo RCSB], [https://www.ebi.ac.uk/pdbsum/5ypo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypo 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=5ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ypo OCA], [https://pdbe.org/5ypo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ypo RCSB], [https://www.ebi.ac.uk/pdbsum/5ypo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ypo 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Shang, Y]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Weng, Z]] | + | [[Category: Shang Y]] |
| - | [[Category: Zhang, M]] | + | [[Category: Weng Z]] |
| - | [[Category: Zhang, R]] | + | [[Category: Zhang M]] |
| - | [[Category: Zhou, Q]] | + | [[Category: Zhang R]] |
| - | [[Category: Zhu, J]] | + | [[Category: Zhou Q]] |
| - | [[Category: Protein binding]]
| + | [[Category: Zhu J]] |
| - | [[Category: Psd-95 sapap phosphorylation synapse]]
| + | |
| 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
The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo.
Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.,Zhu J, Zhou Q, Shang Y, Li H, Peng M, Ke X, Weng Z, Zhang R, Huang X, Li SSC, Feng G, Lu Y, Zhang M Cell Rep. 2017 Dec 26;21(13):3781-3793. doi: 10.1016/j.celrep.2017.11.107. PMID:29281827[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
- ↑ Zhu J, Zhou Q, Shang Y, Li H, Peng M, Ke X, Weng Z, Zhang R, Huang X, Li SSC, Feng G, Lu Y, Zhang M. Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs. Cell Rep. 2017 Dec 26;21(13):3781-3793. doi: 10.1016/j.celrep.2017.11.107. PMID:29281827 doi:http://dx.doi.org/10.1016/j.celrep.2017.11.107
|
