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| | ==GephE in complex with a GABA receptor alpha3 subunit derived double mutant peptide in space group P61== | | ==GephE in complex with a GABA receptor alpha3 subunit derived double mutant peptide in space group P61== |
| - | <StructureSection load='4tk4' size='340' side='right' caption='[[4tk4]], [[Resolution|resolution]] 3.60Å' scene=''> | + | <StructureSection load='4tk4' size='340' side='right'caption='[[4tk4]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tk4]] is a 4 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=4TK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TK4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tk4]] is a 4 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=4TK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TK4 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tk1|4tk1]], [[4tk2|4tk2]], [[4tk3|4tk3]]</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]] 3.601Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gphn, Gph ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4tk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tk4 OCA], [https://pdbe.org/4tk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tk4 RCSB], [https://www.ebi.ac.uk/pdbsum/4tk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tk4 ProSAT]</span></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=4tk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tk4 OCA], [http://pdbe.org/4tk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tk4 RCSB], [http://www.ebi.ac.uk/pdbsum/4tk4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tk4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GEPH_RAT GEPH_RAT]] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.<ref>PMID:8264797</ref> <ref>PMID:9990024</ref> [[http://www.uniprot.org/uniprot/GBRA3_RAT GBRA3_RAT]] GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | + | [https://www.uniprot.org/uniprot/GEPH_RAT GEPH_RAT] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.<ref>PMID:8264797</ref> <ref>PMID:9990024</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 4tk4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4tk4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gephyrin|Gephyrin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Kasaragod, V B]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Maric, H M]] | + | [[Category: Kasaragod VB]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Maric HM]] |
| - | [[Category: Biosynthetic protein]] | + | [[Category: Schindelin H]] |
| - | [[Category: Molybdenum co factor bio synthesis]]
| + | |
| - | [[Category: Neurotransmitter receptor anchoring]]
| + | |
| - | [[Category: Scaffolding protein]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
GEPH_RAT Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.[1] [2]
Publication Abstract from PubMed
gamma-Aminobutyric acid type A and glycine receptors (GABAARs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABAARs are important drug targets regulated by direct interactions with the scaffolding protein gephyrin. Here we deduce the molecular basis of this interaction by chemical, biophysical and structural studies of the gephyrin-GABAAR alpha3 complex, revealing that the N-terminal region of the alpha3 peptide occupies the same binding site as the GlyR beta subunit, whereas the C-terminal moiety, which is conserved among all synaptic GABAAR alpha subunits, engages in unique interactions. Thermodynamic dissections of the gephyrin-receptor interactions identify two residues as primary determinants for gephyrin's subunit preference. This first structural evidence for the gephyrin-mediated synaptic accumulation of GABAARs offers a framework for future investigations into the regulation of inhibitory synaptic strength and for the development of mechanistically and therapeutically relevant compounds targeting the gephyrin-GABAAR interaction.
Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin.,Maric HM, Kasaragod VB, Hausrat TJ, Kneussel M, Tretter V, Stromgaard K, Schindelin H Nat Commun. 2014 Dec 22;5:5767. doi: 10.1038/ncomms6767. PMID:25531214[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kirsch J, Wolters I, Triller A, Betz H. Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature. 1993 Dec 23-30;366(6457):745-8. PMID:8264797 doi:http://dx.doi.org/10.1038/366745a0
- ↑ Stallmeyer B, Schwarz G, Schulze J, Nerlich A, Reiss J, Kirsch J, Mendel RR. The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1333-8. PMID:9990024
- ↑ Maric HM, Kasaragod VB, Hausrat TJ, Kneussel M, Tretter V, Stromgaard K, Schindelin H. Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin. Nat Commun. 2014 Dec 22;5:5767. doi: 10.1038/ncomms6767. PMID:25531214 doi:http://dx.doi.org/10.1038/ncomms6767
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