7N17
Structure of TAX-4_R421W apo open state
Summary for 7N17
| Entry DOI | 10.2210/pdb7n17/pdb |
| Related | 7N15 7N16 |
| EMDB information | 24113 24114 24115 |
| Descriptor | Cyclic nucleotide-gated cation channel, 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE (2 entities in total) |
| Functional Keywords | ion channel, blindness-associated mutation, achromatopsia, phototransduction, transport protein |
| Biological source | Caenorhabditis elegans |
| Total number of polymer chains | 4 |
| Total formula weight | 355533.10 |
| Authors | |
| Primary citation | Zheng, X.,Li, H.,Hu, Z.,Su, D.,Yang, J. Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel. Commun Biol, 5:190-190, 2022 Cited by PubMed Abstract: 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. PubMed: 35233102DOI: 10.1038/s42003-022-03120-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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