3jaf: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3jaf]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JAF FirstGlance]. <br> | <table><tr><td colspan='2'>[[3jaf]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JAF FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3. | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IVM:(2AE,4E,5S,6S,6R,7S,8E,11R,13R,15S,17AR,20R,20AR,20BS)-6-[(2S)-BUTAN-2-YL]-20,20B-DIHYDROXY-5,6,8,19-TETRAMETHYL-17-OXO-3,4,5,6,6,10,11,14,15,17,17A,20,20A,20B-TETRADECAHYDRO-2H,7H-SPIRO[11,15-METHANOFURO[4,3,2-PQ][2,6]BENZODIOXACYCLOOCTADECINE-13,2-PYRAN]-7-YL+2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>IVM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IVM:(2AE,4E,5S,6S,6R,7S,8E,11R,13R,15S,17AR,20R,20AR,20BS)-6-[(2S)-BUTAN-2-YL]-20,20B-DIHYDROXY-5,6,8,19-TETRAMETHYL-17-OXO-3,4,5,6,6,10,11,14,15,17,17A,20,20A,20B-TETRADECAHYDRO-2H,7H-SPIRO[11,15-METHANOFURO[4,3,2-PQ][2,6]BENZODIOXACYCLOOCTADECINE-13,2-PYRAN]-7-YL+2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>IVM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=3jaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jaf OCA], [https://pdbe.org/3jaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jaf RCSB], [https://www.ebi.ac.uk/pdbsum/3jaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jaf 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=3jaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jaf OCA], [https://pdbe.org/3jaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jaf RCSB], [https://www.ebi.ac.uk/pdbsum/3jaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jaf ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/GLRA1_DANRE GLRA1_DANRE] Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).[UniProtKB:P23415]<ref>PMID:10188956</ref> <ref>PMID:26344198</ref> | [https://www.uniprot.org/uniprot/GLRA1_DANRE GLRA1_DANRE] Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).[UniProtKB:P23415]<ref>PMID:10188956</ref> <ref>PMID:26344198</ref> | ||
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== Publication Abstract from PubMed == | |||
The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of glycine receptors has been hindered by a lack of high-resolution structures. Here we report electron cryo-microscopy structures of the zebrafish alpha1 GlyR with strychnine, glycine, or glycine and ivermectin (glycine/ivermectin). Strychnine arrests the receptor in an antagonist-bound closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain 'wrist' interface, and leads to rotation of the transmembrane domain towards the pore axis, occluding the ion conduction pathway. These structures illuminate the GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors. | |||
Glycine receptor mechanism elucidated by electron cryo-microscopy.,Du J, Lu W, Wu S, Cheng Y, Gouaux E Nature. 2015 Sep 7. doi: 10.1038/nature14853. PMID:26344198<ref>PMID:26344198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||