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==Cryo-EM structure of cGMP bound truncated human CNGA3/CNGB3 channel in lipid nanodisc, closed state==
<StructureSection load='8ev8' size='340' side='right'caption='[[8ev8]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ev8]] is a 4 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=8EV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EV8 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]] 3.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</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=8ev8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ev8 OCA], [https://pdbe.org/8ev8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ev8 RCSB], [https://www.ebi.ac.uk/pdbsum/8ev8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ev8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CNGA3_HUMAN CNGA3_HUMAN] Achromatopsia;Cone rod dystrophy. The disease is caused by mutations affecting the gene represented in this entry.  Defects in CNGA3 may be a cause of Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
== Function ==
[https://www.uniprot.org/uniprot/CNGA3_HUMAN CNGA3_HUMAN] Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3 (By similarity). Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones.<ref>PMID:10888875</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclic nucleotide-gated (CNG) channels transduce chemical signals into electrical signals in sensory receptors and neurons. They are activated by cGMP or cAMP, which bind to the cyclic nucleotide-binding domain (CNBD) to open a gate located 50-60 A away in the central cavity. Structures of closed and open vertebrate CNG channels have been solved, but the conformational landscape of this allosteric gating remains to be elucidated and enriched. Here, we report structures of the cGMP-activated human cone photoreceptor CNGA3/CNGB3 channel in closed, intermediate, pre-open and open states in detergent or lipid nanodisc, all with fully bound cGMP. The pre-open and open states are obtained only in the lipid nanodisc, suggesting a critical role of lipids in tuning the energetic landscape of CNGA3/CNGB3 activation. The different states exhibit subunit-unique, incremental and distinct conformational rearrangements that originate in the CNBD, propagate through the gating ring to the transmembrane domain, and gradually open the S6 cavity gate. Our work illustrates a spatial conformational-change wave of allosteric gating of a vertebrate CNG channel by its natural ligand and provides an expanded framework for studying CNG properties and channelopathy.

Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel.,Hu Z, Zheng X, Yang J Nat Commun. 2023 Jul 18;14(1):4284. doi: 10.1038/s41467-023-39971-8. PMID:37463923<ref>PMID:37463923</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ev8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hu Z]]
[[Category: Yang J]]