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Yorodumi- PDB-9yda: Cryo-EM structure of active human green cone opsin in complex wit... -
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Basic information
| Entry | Database: PDB / ID: 9yda | ||||||||||||||||||||||||
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| Title | Cryo-EM structure of active human green cone opsin in complex with chimeric G protein (miniGist) | ||||||||||||||||||||||||
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Keywords | SIGNALING PROTEIN / G protein-coupled receptor / cone opsin | ||||||||||||||||||||||||
| Function / homology | Function and homology informationDefective visual phototransduction due to OPN1MW loss of function / The retinoid cycle in cones (daylight vision) / Opsins / G protein-coupled photoreceptor activity / cellular response to light stimulus / positive regulation of cytokinesis / photoreceptor activity / phototransduction / photoreceptor outer segment / visual perception ...Defective visual phototransduction due to OPN1MW loss of function / The retinoid cycle in cones (daylight vision) / Opsins / G protein-coupled photoreceptor activity / cellular response to light stimulus / positive regulation of cytokinesis / photoreceptor activity / phototransduction / photoreceptor outer segment / visual perception / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / identical protein binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||||||||||||||
Authors | Yao, W. / Fay, J.F. / Farrens, D.L. | ||||||||||||||||||||||||
| Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2025Title: Structure of human green cone opsin yields insights into mechanisms underlying the rapid decay of its active, signaling state. Authors: Weekie Yao / Jonathan F Fay / David L Farrens / ![]() Abstract: Cone opsins enable daylight vision and color discrimination. Like their dim-light cousin rhodopsin (Rho) found in rod cells, they use a covalently attached retinal ligand to sense light and initiate ...Cone opsins enable daylight vision and color discrimination. Like their dim-light cousin rhodopsin (Rho) found in rod cells, they use a covalently attached retinal ligand to sense light and initiate visual phototransduction by activating G proteins. Unfortunately, we know less about their structural properties, in part because their activated state is unstable-cone opsins release their retinal agonist within seconds after light activation, ~100× faster than Rho. To determine what causes this rapid release and how it affects G protein activation, we solved the structure of active-state, wild-type human green cone opsin (GCO) stabilized with a mini-G protein and then compared its structural and biophysical properties to Rho. Our results reveal unique features in the active-state GCO structure. These include i) a larger water channel connected to a larger retinal binding cavity, ii) a larger "hole" near the retinal Schiff base that could facilitate both retinal escape and water access; and iii) a potential anionic residue, E102, that lies within ~3.6 Å of the Schiff base. Our biophysical assays show that neutralizing E102 (mutant GCO) slows retinal release (~8×) from the receptor and increases G protein activation. Surprisingly, our kinetic studies suggest that entropic factors are the main cause for the faster retinal release from activated GCO. These unique attributes in GCO likely facilitate its function in bright daylight. These results support the proposal that rapid retinal release from an active-state cone opsin helps prevent signal saturation and enables rapid resetting of the receptor. | ||||||||||||||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9yda.cif.gz | 244.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9yda.ent.gz | 187.2 KB | Display | PDB format |
| PDBx/mmJSON format | 9yda.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yd/9yda ftp://data.pdbj.org/pub/pdb/validation_reports/yd/9yda | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 72798MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules RA
| #1: Protein | Mass: 40700.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: wild-type human green cone opsin with Rho1D4 tail / Source: (gene. exp.) Homo sapiens (human) / Gene: OPN1MW, GCP / Plasmid: pMT4 / Cell (production host): fibroblast / Cell line (production host): COS-1 / Production host: Chlorocebus aethiops (grivet) / Tissue (production host): kidney / References: UniProt: P04001 |
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| #5: Protein | Mass: 57380.715 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pcDNA3 / Cell (production host): fibroblast / Cell line (production host): COS-1 / Production host: Chlorocebus aethiops (grivet) / Tissue (production host): kidneyReferences: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules BG
| #2: Protein | Mass: 38878.375 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: G beta 1 subunit with Rho1D4 tail / Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Plasmid: pcDNA3 / Cell (production host): fibroblast / Cell line (production host): COS-1 / Production host: Chlorocebus aethiops (grivet) / Tissue (production host): kidney / References: UniProt: P62873 |
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| #3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Plasmid: pcDNA3 / Cell (production host): fibroblast / Cell line (production host): COS-1 / Production host: Chlorocebus aethiops (grivet) / Tissue (production host): kidney / References: UniProt: P59768 |
-Antibody / Non-polymers , 2 types, 2 molecules H

| #4: Antibody | Mass: 27784.896 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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| #6: Chemical | ChemComp-RET / |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Cryo-EM structure of active human green cone opsin in complex with chimeric G protein (miniGist) Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Chlorocebus aethiops (grivet) / Cell: COS-1 / Plasmid: pcDNA3 |
| Buffer solution | pH: 7 |
| Buffer component | Conc.: 20 mM / Name: HEPES / Formula: C8H18N2O4S |
| Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
| Microscopy | Model: TFS GLACIOS |
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| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2100 nm / Nominal defocus min: 200 nm |
| Image recording | Electron dose: 37.2 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of real images: 4190 |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
| 3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 639873 / Symmetry type: POINT | |||||||||||||||||||||
| Atomic model building | Source name: AlphaFold / Type: in silico model |
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About Yorodumi



Homo sapiens (human)

United States, 1items
Citation
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FIELD EMISSION GUN