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Yorodumi- EMDB-23254: CryoEM structure of the HCMV Trimer gHgLgO in complex with human ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23254 | |||||||||
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Title | CryoEM structure of the HCMV Trimer gHgLgO in complex with human Transforming growth factor beta receptor type 3 and neutralizing fabs 13H11 and MSL-109 | |||||||||
Map data | Composite map of Trimer-TGFBR3 complex bound to fabs 13H11 and Msl-109 used for model refinements | |||||||||
Sample |
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Function / homology | Function and homology information : / response to luteinizing hormone / epicardium-derived cardiac fibroblast cell development / transforming growth factor beta receptor activity, type III / transforming growth factor beta receptor complex assembly / : / inhibin-betaglycan-ActRII complex / muscular septum morphogenesis / definitive erythrocyte differentiation / response to follicle-stimulating hormone ...: / response to luteinizing hormone / epicardium-derived cardiac fibroblast cell development / transforming growth factor beta receptor activity, type III / transforming growth factor beta receptor complex assembly / : / inhibin-betaglycan-ActRII complex / muscular septum morphogenesis / definitive erythrocyte differentiation / response to follicle-stimulating hormone / response to prostaglandin E / vasculogenesis involved in coronary vascular morphogenesis / transforming growth factor beta receptor activity / secondary palate development / ventricular compact myocardium morphogenesis / regulation of transforming growth factor beta receptor signaling pathway / cardiac epithelial to mesenchymal transition / transforming growth factor beta receptor binding / type II transforming growth factor beta receptor binding / regulation of protein binding / heart trabecula morphogenesis / activin binding / heart trabecula formation / glycosaminoglycan binding / transforming growth factor beta binding / definitive hemopoiesis / ventricular cardiac muscle tissue morphogenesis / cardiac muscle cell proliferation / ventricular septum morphogenesis / fibroblast growth factor binding / positive regulation of transforming growth factor beta receptor signaling pathway / outflow tract morphogenesis / SMAD binding / plasma membrane => GO:0005886 / epithelial to mesenchymal transition / vasculogenesis / animal organ regeneration / BMP signaling pathway / coreceptor activity / heart morphogenesis / positive regulation of cardiac muscle cell proliferation / transforming growth factor beta receptor signaling pathway / host cell endosome membrane / extracellular matrix / HCMV Late Events / liver development / PDZ domain binding / negative regulation of transforming growth factor beta receptor signaling pathway / HCMV Early Events / negative regulation of epithelial cell proliferation / cell migration / heparin binding / host cell Golgi apparatus / angiogenesis / entry receptor-mediated virion attachment to host cell / receptor complex / response to hypoxia / intracellular signal transduction / symbiont entry into host cell / immune response / fusion of virus membrane with host plasma membrane / external side of plasma membrane / viral envelope / host cell plasma membrane / virion membrane / cell surface / extracellular space / extracellular exosome / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Human cytomegalovirus HHV-5 / Homo sapiens (human) / Human cytomegalovirus (strain Merlin) / Human cytomegalovirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Kschonsak M / Rouge L / Arthur CP / Hoangdung H / Patel N / Kim I / Johnson M / Kraft E / Rohou AL / Gill A ...Kschonsak M / Rouge L / Arthur CP / Hoangdung H / Patel N / Kim I / Johnson M / Kraft E / Rohou AL / Gill A / Martinez-Martin N / Payandeh J / Ciferri C | |||||||||
Citation | Journal: Cell / Year: 2021 Title: Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry. Authors: Marc Kschonsak / Lionel Rougé / Christopher P Arthur / Ho Hoangdung / Nidhi Patel / Ingrid Kim / Matthew C Johnson / Edward Kraft / Alexis L Rohou / Avinash Gill / Nadia Martinez-Martin / ...Authors: Marc Kschonsak / Lionel Rougé / Christopher P Arthur / Ho Hoangdung / Nidhi Patel / Ingrid Kim / Matthew C Johnson / Edward Kraft / Alexis L Rohou / Avinash Gill / Nadia Martinez-Martin / Jian Payandeh / Claudio Ciferri / Abstract: Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind ...Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRα) and transforming growth factor beta receptor 3 (TGFβR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRα and TGFβR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRα and TGFβR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRα interaction has an inhibitory effect on PDGFRα signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23254.map.gz | 91.9 MB | EMDB map data format | |
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Header (meta data) | emd-23254-v30.xml emd-23254.xml | 36.9 KB 36.9 KB | Display Display | EMDB header |
Images | emd_23254.png | 73.1 KB | ||
Others | emd_23254_additional_1.map.gz emd_23254_additional_2.map.gz emd_23254_additional_3.map.gz emd_23254_additional_4.map.gz emd_23254_additional_5.map.gz | 91.3 MB 91.2 MB 91.2 MB 91.3 MB 91.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23254 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23254 | HTTPS FTP |
-Validation report
Summary document | emd_23254_validation.pdf.gz | 188.7 KB | Display | EMDB validaton report |
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Full document | emd_23254_full_validation.pdf.gz | 188.2 KB | Display | |
Data in XML | emd_23254_validation.xml.gz | 502 B | Display | |
Data in CIF | emd_23254_validation.cif.gz | 373 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23254 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23254 | HTTPS FTP |
-Related structure data
Related structure data | 7lbgMC 7lbeC 7lbfC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23254.map.gz / Format: CCP4 / Size: 98.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Composite map of Trimer-TGFBR3 complex bound to fabs 13H11 and Msl-109 used for model refinements | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1948 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Overall Trimer-TGFBR3-13H11-MSL109 map before focussed refinements, non-sharpened used...
File | emd_23254_additional_1.map | ||||||||||||
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Annotation | Overall Trimer-TGFBR3-13H11-MSL109 map before focussed refinements, non-sharpened used for composite map generation | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed map on gO, gL, TGFBR3-OD2 domain, sharpened...
File | emd_23254_additional_2.map | ||||||||||||
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Annotation | Focussed map on gO, gL, TGFBR3-OD2 domain, sharpened used for composite map generation | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed map on gH and Fv regions of...
File | emd_23254_additional_3.map | ||||||||||||
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Annotation | Focussed map on gH and Fv regions of both fabs, sharpened used for composite map generation | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed map on gO, gL, TGFBR3-OD2 domain, non-sharpened
File | emd_23254_additional_4.map | ||||||||||||
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Annotation | Focussed map on gO, gL, TGFBR3-OD2 domain, non-sharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed map on gH and Fv regions of both fabs, non-sharpened
File | emd_23254_additional_5.map | ||||||||||||
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Annotation | Focussed map on gH and Fv regions of both fabs, non-sharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : HCMV Trimer gHgLgO bound to human receptor TGFbR3 and neutralizin...
+Supramolecule #1: HCMV Trimer gHgLgO bound to human receptor TGFbR3 and neutralizin...
+Supramolecule #2: HCMV Trimer gHgLgO
+Supramolecule #3: neutralizing fabs 13H11 and MSL-109
+Macromolecule #1: Envelope glycoprotein H
+Macromolecule #2: Envelope glycoprotein L
+Macromolecule #3: Envelope glycoprotein O
+Macromolecule #4: Transforming growth factor beta receptor type 3
+Macromolecule #5: Fab 13H11 light chain
+Macromolecule #6: Fab 13H11 heavy chain
+Macromolecule #7: Fab MSL-109 light chain
+Macromolecule #8: Fab MSL-109 heavy chain
+Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | 2D array |
-Sample preparation
Concentration | 0.5 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: LEICA EM GP / Details: blot for 3.5 seconds before plunging. | |||||||||
Details | This sample was monodisperse |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Number grids imaged: 1 / Number real images: 19993 / Average exposure time: 10.0 sec. / Average electron dose: 50.0 e/Å2 / Details: Images were collected in 50 frames every 0.2 s |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal magnification: 165000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-7lbg: |