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Yorodumi- PDB-8etp: Cryo-EM structure of cGMP bound closed state of human CNGA3/CNGB3... -
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-Basic information
Entry | Database: PDB / ID: 8etp | ||||||
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Title | Cryo-EM structure of cGMP bound closed state of human CNGA3/CNGB3 channel in GDN | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Heterotetramer / ligand-bound | ||||||
Function / homology | Function and homology information inorganic cation import across plasma membrane / intracellular cyclic nucleotide activated cation channel complex / intracellularly cGMP-activated cation channel activity / axon initial segment / intracellularly cAMP-activated cation channel activity / myosin binding / monoatomic cation transmembrane transport / monoatomic cation transport / glial cell projection / response to magnesium ion ...inorganic cation import across plasma membrane / intracellular cyclic nucleotide activated cation channel complex / intracellularly cGMP-activated cation channel activity / axon initial segment / intracellularly cAMP-activated cation channel activity / myosin binding / monoatomic cation transmembrane transport / monoatomic cation transport / glial cell projection / response to magnesium ion / ligand-gated monoatomic ion channel activity / photoreceptor outer segment / cGMP binding / transmembrane transporter complex / response to cAMP / visual perception / perikaryon / cadherin binding / dendrite / protein-containing complex binding / signal transduction / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.52 Å | ||||||
Authors | Hu, Z. / Zheng, X. / Yang, J. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel. Authors: Zhengshan Hu / Xiangdong Zheng / Jian Yang / Abstract: 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- ...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 Å 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8etp.cif.gz | 341 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8etp.ent.gz | 270.7 KB | Display | PDB format |
PDBx/mmJSON format | 8etp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8etp_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8etp_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8etp_validation.xml.gz | 64.1 KB | Display | |
Data in CIF | 8etp_validation.cif.gz | 93 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/et/8etp ftp://data.pdbj.org/pub/pdb/validation_reports/et/8etp | HTTPS FTP |
-Related structure data
Related structure data | 28595MC 8eu3C 8eucC 8ev8C 8ev9C 8evaC 8evbC 8evcC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 78937.930 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CNGA3, CNCG3 / Production host: Homo sapiens (human) / References: UniProt: Q16281 #2: Protein | | Mass: 92289.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CNGB3 / Production host: Homo sapiens (human) / References: UniProt: Q9NQW8 #3: Sugar | #4: Chemical | ChemComp-PCG / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human cone photoreceptor heterotetrameric CNG channel CNGA3/CNGB3 in complex with cGMP Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8.58 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: OTHER / Nominal defocus max: 1900 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 55.03 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 74921 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 68.61 Å2 | ||||||||||||||||||||||||
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