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| ==Structure of PSD-95/MAP1A complex reveals unique target recognition mode of MAGUK GK domain== | | ==Structure of PSD-95/MAP1A complex reveals unique target recognition mode of MAGUK GK domain== |
- | <StructureSection load='5gnv' size='340' side='right' caption='[[5gnv]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='5gnv' size='340' side='right'caption='[[5gnv]], [[Resolution|resolution]] 2.60Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5gnv]] 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=5GNV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gnv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=5GNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GNV FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.596Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dlg4, Dlgh4, Psd95 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5gnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gnv OCA], [http://pdbe.org/5gnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gnv RCSB], [http://www.ebi.ac.uk/pdbsum/5gnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gnv 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=5gnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gnv OCA], [https://pdbe.org/5gnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gnv RCSB], [https://www.ebi.ac.uk/pdbsum/5gnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gnv 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/MAP1A_MOUSE MAP1A_MOUSE]] Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. | + | [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 5gnv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5gnv" 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: Buffalo rat]] | + | [[Category: Large Structures]] |
- | [[Category: Shang, Y]] | + | [[Category: Mus musculus]] |
- | [[Category: Xia, Y]] | + | [[Category: Rattus norvegicus]] |
- | [[Category: Zhu, J]] | + | [[Category: Shang Y]] |
- | [[Category: Zhu, R]] | + | [[Category: Xia Y]] |
- | [[Category: Binding-induced folding]] | + | [[Category: Zhu J]] |
- | [[Category: Peptide binding protein]] | + | [[Category: Zhu R]] |
| 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 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-A resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs.
Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.,Xia Y, Shang Y, Zhang R, Zhu J Biochem J. 2017 Aug 10;474(16):2817-2828. doi: 10.1042/BCJ20170356. PMID:28701415[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
- ↑ Xia Y, Shang Y, Zhang R, Zhu J. Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain. Biochem J. 2017 Aug 10;474(16):2817-2828. doi: 10.1042/BCJ20170356. PMID:28701415 doi:http://dx.doi.org/10.1042/BCJ20170356
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