4tk3: Difference between revisions
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==Geph E in complex with a GABA receptor alpha3 derived double mutant peptide in spacegroup P21212== | ==Geph E in complex with a GABA receptor alpha3 derived double mutant peptide in spacegroup P21212== | ||
<StructureSection load='4tk3' size='340' side='right' caption='[[4tk3]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='4tk3' size='340' side='right'caption='[[4tk3]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4tk3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TK3 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4tk3]] 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=4TK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TK3 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tk3 OCA], [https://pdbe.org/4tk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4tk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tk3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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;"> | |||
== 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<ref>PMID:25531214</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4tk3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Gephyrin|Gephyrin]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: | [[Category: Kasaragod VB]] | ||
[[Category: | [[Category: Maric HM]] | ||
[[Category: | [[Category: Schindelin H]] | ||
Latest revision as of 10:19, 27 September 2023
Geph E in complex with a GABA receptor alpha3 derived double mutant peptide in spacegroup P21212Geph E in complex with a GABA receptor alpha3 derived double mutant peptide in spacegroup P21212
Structural highlights
FunctionGEPH_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 PubMedgamma-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 AlsoReferences
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