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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Local refined cryoEM map of CXCL1-KSHV ORF74 region | |||||||||
Map data | Local refined map of KSHV ORF74-CXCL1 region | |||||||||
Sample |
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Keywords | KSHV vGPCR / Viral GPCR / KSHV ORF74 / CXCL1-ORF74 / ORF74 Active / CXCL1 bound ORF74 / CXCL1-KSHV ORF74-Gi-scFv16 / VIRAL PROTEIN | |||||||||
| Biological species | ![]() Human gammaherpesvirus 8 / Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Sahoo B / Seo HD / Dai X / Jung J | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2025Title: Structural basis for ligand promiscuity and high signaling activity of Kaposi's Sarcoma-associated Herpesvirus-encoded GPCR. Authors: Jun Bae Park / Bibekananda Sahoo / Amita Rani Sahoo / Dokyun Kim / Hogyu David Seo / James Bowman / Mi-Jeong Kwak / Sophia Suh / Matthias Buck / Xinghong Dai / Jae U Jung / ![]() Abstract: Kaposi's Sarcoma-associated Herpesvirus encodes ORF74, a viral G protein-coupled receptor homologous to CXCR2, which plays a crucial role in Kaposi's Sarcoma development through its high basal ...Kaposi's Sarcoma-associated Herpesvirus encodes ORF74, a viral G protein-coupled receptor homologous to CXCR2, which plays a crucial role in Kaposi's Sarcoma development through its high basal signaling activity. Our cryoEM analysis of ORF74 in ligand-free, BRIL-fused ligand-free, and CXCL1/Gi-bound forms elucidates its ligand-independent signaling activity. A widely open, static extracellular cavity facilitates ligand promiscuity by enabling dynamic access and diverse binding modes. Structural alterations in CWxP, E/DRY, and NPxxY micro-switches stabilize the active conformation, leading to constitutive signaling. Metadynamics simulations reveal a dynamic ensemble between local switch structures corresponding to the inactive and active states, supporting spontaneous activation. CXCR2-ORF74 chimeras highlight intracellular loops 2 and 3 as key modulators of basal and agonist-induced activity. This study defines the structural basis of ORF74's ligand promiscuity, spontaneous activation, and high basal signaling, providing insights into its role in viral oncogenesis. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_48097.map.gz | 32.3 MB | EMDB map data format | |
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| Header (meta data) | emd-48097-v30.xml emd-48097.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_48097_fsc.xml | 12 KB | Display | FSC data file |
| Images | emd_48097.png | 62 KB | ||
| Filedesc metadata | emd-48097.cif.gz | 4.5 KB | ||
| Others | emd_48097_half_map_1.map.gz emd_48097_half_map_2.map.gz | 30.5 MB 30.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-48097 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-48097 | HTTPS FTP |
-Validation report
| Summary document | emd_48097_validation.pdf.gz | 564.2 KB | Display | EMDB validaton report |
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| Full document | emd_48097_full_validation.pdf.gz | 563.7 KB | Display | |
| Data in XML | emd_48097_validation.xml.gz | 20.4 KB | Display | |
| Data in CIF | emd_48097_validation.cif.gz | 26.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-48097 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-48097 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_48097.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Local refined map of KSHV ORF74-CXCL1 region | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.66 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: Half map A for local refined KSHV ORF74-CXCL1 region
| File | emd_48097_half_map_1.map | ||||||||||||
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| Annotation | Half map A for local refined KSHV ORF74-CXCL1 region | ||||||||||||
| Projections & Slices |
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| Density Histograms |
-Half map: Half map B for local refined KSHV ORF74-CXCL1 region
| File | emd_48097_half_map_2.map | ||||||||||||
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| Annotation | Half map B for local refined KSHV ORF74-CXCL1 region | ||||||||||||
| Projections & Slices |
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| Density Histograms |
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Sample components
-Entire : CXCL1 bound to KSHV ORF74
| Entire | Name: CXCL1 bound to KSHV ORF74 |
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| Components |
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-Supramolecule #1: CXCL1 bound to KSHV ORF74
| Supramolecule | Name: CXCL1 bound to KSHV ORF74 / type: complex / ID: 1 / Parent: 0 |
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| Molecular weight | Theoretical: 140 KDa |
-Supramolecule #2: KSHV ORF74
| Supramolecule | Name: KSHV ORF74 / type: complex / ID: 2 / Parent: 1 |
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| Source (natural) | Organism: ![]() Human gammaherpesvirus 8 |
-Supramolecule #3: CXCL1
| Supramolecule | Name: CXCL1 / type: complex / ID: 3 / Parent: 1 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 10 mg/mL |
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| Buffer | pH: 7.5 / Component - Concentration: 10.0 mM / Component - Formula: C8H18N2O4S / Component - Name: HEPES Details: 10 mM HEPES pH 7.5, 150 mM NaCl, 0.001% (w/v) LMNG, 0.0001% (w/v) CHS, 0.001% (w/v) GDN |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Human gammaherpesvirus 8
Homo sapiens (human)
Authors
United States, 1 items
Citation






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Processing
FIELD EMISSION GUN

