View source for 9ctq


==Best1 + GABA open state==
<StructureSection load='9ctq' size='340' side='right'caption='[[9ctq]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ctq]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9CTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CTQ 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]] 2.41&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=9ctq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ctq OCA], [https://pdbe.org/9ctq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ctq RCSB], [https://www.ebi.ac.uk/pdbsum/9ctq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ctq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BEST1_HUMAN BEST1_HUMAN] Adult-onset foveomacular vitelliform dystrophy;MRCS syndrome;Autosomal recessive bestrophinopathy;Best vitelliform macular dystrophy;Nanophthalmos;Autosomal dominant vitreoretinochoroidopathy;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/BEST1_HUMAN BEST1_HUMAN] Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+) (PubMed:11904445, PubMed:12907679, PubMed:18179881, PubMed:18400985, PubMed:19853238, PubMed:21330666, PubMed:26200502, PubMed:26720466, PubMed:35789156). Allows the movement of chloride and hydrogencarbonate (PubMed:11904445, PubMed:12907679, PubMed:18179881, PubMed:18400985, PubMed:19853238, PubMed:21330666, PubMed:26200502, PubMed:26720466, PubMed:35789156). Found in a partially open conformation leading to significantly smaller chloride movement (PubMed:35789156). Upon F2R/PAR-1 activation, the sequestered calcium is released into the cytosol of astrocytes, leading to the (Ca2+)-dependent release of L-glutamate into the synaptic cleft that targets the neuronal postsynaptic GRIN2A/NMDAR receptor resulting in the synaptic plasticity regulation (By similarity). Upon activation of the norepinephrine-alpha-1 adrenergic receptor signaling pathway, transports as well D-serine than L-glutamate in a (Ca2+)-dependent manner, leading to activation of adjacent NMDAR receptors and therefore regulates the heterosynaptic long-term depression and metaplasticity during initial memory acquisition (By similarity). Releases the 4-aminobutanoate neurotransmitter in a (Ca2+)-dependent manner, and participates in its tonic release from cerebellar glial cells (By similarity).[UniProtKB:O88870]<ref>PMID:11904445</ref> <ref>PMID:12907679</ref> <ref>PMID:18179881</ref> <ref>PMID:18400985</ref> <ref>PMID:19853238</ref> <ref>PMID:21330666</ref> <ref>PMID:26200502</ref> <ref>PMID:26720466</ref> <ref>PMID:35789156</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bestrophin-1 (Best1) is an anion channel genetically linked to vision-threatening retinal degenerative channelopathies. Here, we identify interactions between Best1 and both isoforms of glutamic acid decarboxylases (GAD65 and GAD67), elucidate the distinctive influences of GAD65 and GAD67 on Best1's permeability to various anions/neurotransmitters, discover the functionality of Best1 as a gamma-Aminobutyric acid (GABA) type A receptor, and solve the structure of GABA-bound Best1. GAD65 and GAD67 both promote Best1-mediated Cl(-) currents, but only GAD65 drastically enhances the permeability of Best1 to glutamate and GABA, for which GAD67 has no effect. GABA binds to Best1 on an extracellular site and stimulates Best1-mediated Cl(-) currents at the nano-molar concentration level. The physiological role of GAD65 as a cell type-specific binding partner and facilitator of Best1 is demonstrated in retinal pigment epithelial cells. Together, our results reveal critical regulators of Best1 and inform a network of membrane transport metabolons formed between bestrophin channels and glutamate metabolic enzymes.

GAD65 tunes the functions of Best1 as a GABA receptor and a neurotransmitter conducting channel.,Wang J, Owji AP, Kittredge A, Clark Z, Zhang Y, Yang T Nat Commun. 2024 Sep 14;15(1):8051. doi: 10.1038/s41467-024-52039-5. PMID:39277606<ref>PMID:39277606</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ctq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kittredge A]]
[[Category: Owji AP]]
[[Category: Yang T]]
[[Category: Zhang Y]]