View source for 7n17


==Structure of TAX-4_R421W apo open state==
<StructureSection load='7n17' size='340' side='right'caption='[[7n17]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N17 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPL:1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>CPL</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=7n17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n17 OCA], [https://pdbe.org/7n17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n17 RCSB], [https://www.ebi.ac.uk/pdbsum/7n17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n17 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often unclear. We investigated the structural basis and molecular/cellular effects of R410W, an achromatopsia-associated, presumed loss-of-function mutation in human CNGA3. Cryo-EM structures of the Caenorhabditis elegans TAX-4 CNG channel carrying the analogous mutation, R421W, show that most apo channels are open. R421, located in the gating ring, interacts with the S4 segment in the closed state. R421W disrupts this interaction, destabilizes the closed state, and stabilizes the open state. CNGA3_R410W/CNGB3 and TAX4_R421W channels are spontaneously active without cGMP and induce cell death, suggesting cone degeneration triggered by spontaneous CNG channel activity as a possible cause of achromatopsia. Our study sheds new light on CNG channel allosteric gating, provides an impetus for a reevaluation of reported loss-of-function CNG channel missense disease mutations, and has implications for mutation-specific treatment of retinopathy.

Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel.,Zheng X, Li H, Hu Z, Su D, Yang J Commun Biol. 2022 Mar 1;5(1):190. doi: 10.1038/s42003-022-03120-6. PMID:35233102<ref>PMID:35233102</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7n17" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Hu Z]]
[[Category: Li H]]
[[Category: Su D]]
[[Category: Yang J]]
[[Category: Zheng X]]