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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24114 | |||||||||
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Title | Structure of TAX-4_R421W apo closed state | |||||||||
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Function / homology | ![]() detection of carbon dioxide / detection of chemical stimulus involved in sensory perception / ciliary inversin compartment / Activation of the phototransduction cascade / Inactivation, recovery and regulation of the phototransduction cascade / VxPx cargo-targeting to cilium / thermosensory behavior / positive regulation of growth rate / olfactory behavior / aerotaxis ...detection of carbon dioxide / detection of chemical stimulus involved in sensory perception / ciliary inversin compartment / Activation of the phototransduction cascade / Inactivation, recovery and regulation of the phototransduction cascade / VxPx cargo-targeting to cilium / thermosensory behavior / positive regulation of growth rate / olfactory behavior / aerotaxis / chemosensory behavior / intracellular cyclic nucleotide activated cation channel complex / G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger / multicellular organismal reproductive process / intracellularly cGMP-activated cation channel activity / cation channel complex / response to oxygen levels / intracellularly cAMP-activated cation channel activity / thermotaxis / non-motile cilium / regulation of neuron differentiation / regulation of axon extension / negative regulation of cGMP-mediated signaling / voltage-gated potassium channel activity / monoatomic cation transmembrane transport / phototransduction / cGMP binding / response to hyperoxia / neuron projection morphogenesis / calcium-mediated signaling / chemotaxis / dendrite / positive regulation of gene expression / protein-containing complex binding / positive regulation of transcription by RNA polymerase II / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Zheng X / Li H / Hu Z / Su D / Yang J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and functional characterization of an achromatopsia-associated mutation in a phototransduction channel. Authors: Xiangdong Zheng / Huan Li / Zhengshan Hu / Deyuan Su / Jian Yang / ![]() 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 ...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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 93.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.3 KB 13.3 KB | Display Display | ![]() |
Images | ![]() | 176.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7n16MC ![]() 7n15C ![]() 7n17C C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Cyclic nucleotide-gated channel TAX-4 with R421W mutation
Entire | Name: Cyclic nucleotide-gated channel TAX-4 with R421W mutation |
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Components |
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-Supramolecule #1: Cyclic nucleotide-gated channel TAX-4 with R421W mutation
Supramolecule | Name: Cyclic nucleotide-gated channel TAX-4 with R421W mutation type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Cyclic nucleotide-gated cation channel
Macromolecule | Name: Cyclic nucleotide-gated cation channel / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 84.334914 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GGGGSMSTAE PAPDPTNPST SGLAPTTNGI GSPPPTASAA TKFSILTKFL RRKNQVHTTT AQQNEFMQKY MPNGNSNAVQ PAATGGQPA SSDGGSAIEV PPPKESYAVR IRKYLANYTQ DPSTDNFYYW TCVVTVAYIY NLLFVIARQV FNDLIGPSSQ S LCRFYNGT ...String: GGGGSMSTAE PAPDPTNPST SGLAPTTNGI GSPPPTASAA TKFSILTKFL RRKNQVHTTT AQQNEFMQKY MPNGNSNAVQ PAATGGQPA SSDGGSAIEV PPPKESYAVR IRKYLANYTQ DPSTDNFYYW TCVVTVAYIY NLLFVIARQV FNDLIGPSSQ S LCRFYNGT LNSTTQVECT YNMLTNMKEM PTYSQYPDLG WSKYWHFRML WVFFDLLMDC VYLIDTFLNY RMGYMDQGLV VR EAEKVTK AYWQSKQYRI DGISLIPLDY ILGWPIPYIN WRGLPILRLN RLIRYKRVRN CLERTETRSS MPNAFRVVVV VWY IVIIIH WNACLYFWIS EWIGLGTDAW VYGHLNKQSL PDDITDTLLR RYVYSFYWST LILTTIGEVP SPVRNIEYAF VTLD LMCGV LIFATIVGNV GSMISNMSAA WTEFQNKMDG IKQYMELRKV SKQLEIRVIK WFDYLWTNKQ SLSDQQVLKV LPDKL QAEI AMQVHFETLR KVRIFQDCEA GLLAELVLKL QLQVFSPGDF ICKKGDIGRE MYIVKRGRLQ VVDDDGKKVF VTLQEG SVF GELSILNIAG SKNGNRRTAN VRSVGYTDLF VLSKTDLWNA LREYPDARKL LLAKGREILK KDNLLDENAP EEQKTVE EI AEHLNNAVKV LQTRMARLIV EHSSTEGKLM KRIEMLEKHL SRYKALARRQ KTMHGVSIDG GDISTDGVDE RVRPPRLR Q TKTIDLPTGT ESESLLK |
-Macromolecule #2: 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
Macromolecule | Name: 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 2 / Number of copies: 16 / Formula: CPL |
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Molecular weight | Theoretical: 758.06 Da |
Chemical component information | ![]() ChemComp-CPL: |
-Macromolecule #3: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 3 / Number of copies: 1 |
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Molecular weight | Theoretical: 22.99 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Grid | Model: C-flat-1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 58.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |