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Yorodumi- PDB-7lbg: CryoEM structure of the HCMV Trimer gHgLgO in complex with human ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7lbg | ||||||
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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 | ||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / virus / receptor / complex / neutralizing antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | ||||||
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 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
Authors | Kschonsak, M. / Rouge, L. / Arthur, C.P. / Hoangdung, H. / Patel, N. / Kim, I. / Johnson, M. / Kraft, E. / Rohou, A.L. / Gill, A. ...Kschonsak, M. / Rouge, L. / Arthur, C.P. / Hoangdung, H. / Patel, N. / Kim, I. / Johnson, M. / Kraft, E. / Rohou, A.L. / 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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7lbg.cif.gz | 356.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lbg.ent.gz | 280.8 KB | Display | PDB format |
PDBx/mmJSON format | 7lbg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7lbg_validation.pdf.gz | 616.3 KB | Display | wwPDB validaton report |
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Full document | 7lbg_full_validation.pdf.gz | 624.6 KB | Display | |
Data in XML | 7lbg_validation.xml.gz | 39 KB | Display | |
Data in CIF | 7lbg_validation.cif.gz | 64 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lb/7lbg ftp://data.pdbj.org/pub/pdb/validation_reports/lb/7lbg | HTTPS FTP |
-Related structure data
Related structure data | 23254MC 7lbeC 7lbfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Envelope glycoprotein ... , 3 types, 3 molecules ABC
#1: Protein | Mass: 87311.273 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human cytomegalovirus (strain Merlin) / Strain: Merlin / Gene: gH, UL75 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: Q6SW67 |
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#2: Protein | Mass: 30846.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human cytomegalovirus (strain Merlin) / Strain: Merlin / Gene: gL, UL115 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: F5HCH8 |
#3: Protein | Mass: 58298.504 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human cytomegalovirus / Gene: UL74 / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: Q8BCU3 |
-Protein , 1 types, 1 molecules D
#4: Protein | Mass: 87362.203 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TGFBR3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q03167 |
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-Antibody , 4 types, 4 molecules EFGH
#5: Antibody | Mass: 25780.020 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
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#6: Antibody | Mass: 26600.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
#7: Antibody | Mass: 28355.809 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
#8: Antibody | Mass: 27547.818 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
-Sugars , 3 types, 19 molecules
#9: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#10: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
#11: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: 2D ARRAY / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Value: 0.36 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: blot for 3.5 seconds before plunging |
-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: BRIGHT FIELD / Nominal magnification: 165000 X |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 19993 / Details: Images were collected in 50 frames every 0.2 s |
Image scans | Movie frames/image: 50 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2780519 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2737199 Details: Used a score threshold of 0.25 for final 3D reconstruction. Map used for model refinements is a composite map after combining 2 focussed maps with PHENIX Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |