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- EMDB-25686: CryoEM structure of the HCMV Pentamer gH/gL/UL128/UL130/UL131A in... -
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Open data
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Basic information
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Title | CryoEM structure of the HCMV Pentamer gH/gL/UL128/UL130/UL131A in complex with THBD and neutralizing fabs MSL-109 and 13H11 | |||||||||
![]() | Composite map obtained by combining focused, sharpened maps. Map used for model building and refinements. | |||||||||
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Function / homology | ![]() blood coagulation, common pathway / apicolateral plasma membrane / negative regulation of blood coagulation / serine-type endopeptidase complex / zymogen activation / vacuolar membrane / response to X-ray / negative regulation of platelet activation / negative regulation of fibrinolysis / Common Pathway of Fibrin Clot Formation ...blood coagulation, common pathway / apicolateral plasma membrane / negative regulation of blood coagulation / serine-type endopeptidase complex / zymogen activation / vacuolar membrane / response to X-ray / negative regulation of platelet activation / negative regulation of fibrinolysis / Common Pathway of Fibrin Clot Formation / response to cAMP / female pregnancy / Cell surface interactions at the vascular wall / transmembrane signaling receptor activity / blood coagulation / signaling receptor activity / host cell endosome / host cell Golgi apparatus / response to lipopolysaccharide / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / external side of plasma membrane / viral envelope / calcium ion binding / host cell plasma membrane / virion membrane / cell surface / proteolysis / extracellular space / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Kschonsak M / Johnson MC / Schelling R / Green EM / Rouge L / Ho H / Patel N / Kilic C / Kraft E / Arthur CP ...Kschonsak M / Johnson MC / Schelling R / Green EM / Rouge L / Ho H / Patel N / Kilic C / Kraft E / Arthur CP / Rohou AL / Comps-Agrar L / Martinez-Martin N / Perez L / Payandeh J / Ciferri C | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Structural basis for HCMV Pentamer receptor recognition and antibody neutralization. Authors: Marc Kschonsak / Matthew C Johnson / Rachel Schelling / Evan M Green / Lionel Rougé / Hoangdung Ho / Nidhi Patel / Cem Kilic / Edward Kraft / Christopher P Arthur / Alexis L Rohou / ...Authors: Marc Kschonsak / Matthew C Johnson / Rachel Schelling / Evan M Green / Lionel Rougé / Hoangdung Ho / Nidhi Patel / Cem Kilic / Edward Kraft / Christopher P Arthur / Alexis L Rohou / Laetitia Comps-Agrar / Nadia Martinez-Martin / Laurent Perez / Jian Payandeh / Claudio Ciferri / ![]() ![]() Abstract: Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial ...Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 13 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 59.9 KB 59.9 KB | Display Display | ![]() |
Images | ![]() | 83.3 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 226.2 MB 165.7 MB 165.7 MB 8.2 MB 226.4 MB 165.7 MB 165.7 MB 12.3 MB 165.5 MB 13.7 MB 165.6 MB 226.3 MB 165.6 MB 165.7 MB 8.5 MB 226.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 340.2 KB | Display | ![]() |
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Full document | ![]() | 339.8 KB | Display | |
Data in XML | ![]() | 7 KB | Display | |
Data in CIF | ![]() | 8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7t4rMC ![]() 7t4qC ![]() 7t4sC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | Composite map obtained by combining focused, sharpened maps. Map used for model building and refinements. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0726 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
+Additional map: Non-sharpened, full map of overall map (not focused).
+Additional map: Half map 1 of focused gH-gL (A) region.
+Additional map: Half map 2 of focused gH-gL (A) region.
+Additional map: Density modified map of focused gH-gL (A) map...
+Additional map: Non-sharpened, full map of focused gH-gL (B) region.
+Additional map: Half map 1 of focused gH-gL (B) region.
+Additional map: Half map 2 of focused gH-gL (B) region.
+Additional map: Density modified map of overall map (not focused)...
+Additional map: Half map 1 of overall map (not focused).
+Additional map: Density modified map of focused THBD-ULs map used...
+Additional map: Half map 2 of overall map (not focused).
+Additional map: Non-sharpened, full map of focused THBD-ULs region.
+Additional map: Half map 1 of focused THBD-ULs region.
+Additional map: Half map 2 of focused THBD-ULs region.
+Additional map: Density modified map of focused gH-gL (B) map...
+Additional map: Non-sharpened, full map of focused gH-gL (A) region.
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Sample components
+Entire : Complex of 2x HCMV Pentamer gH, gL, UL128, UL130, UL131A bound to...
+Supramolecule #1: Complex of 2x HCMV Pentamer gH, gL, UL128, UL130, UL131A bound to...
+Macromolecule #1: Thrombomodulin
+Macromolecule #2: Envelope glycoprotein H
+Macromolecule #3: Envelope glycoprotein L
+Macromolecule #4: Envelope protein UL128
+Macromolecule #5: Envelope glycoprotein UL130
+Macromolecule #6: Envelope protein UL131A
+Macromolecule #7: Fab 13H11 heavy chain
+Macromolecule #8: Fab 13H11 light chain
+Macromolecule #9: Fab MSL-109 light chain
+Macromolecule #10: 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.6 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: UltrAuFoil R0.6/1 / Material: GOLD / Mesh: 300 Details: The grid was incubated with a thiol reactive self-assembling reaction mixture of 4mM monothiolalkane(C11)PEG6-OH (11-mercaptoundecyl) hexaethyleneglycol, (SPT-0011P6, SensoPath Technologies, ...Details: The grid was incubated with a thiol reactive self-assembling reaction mixture of 4mM monothiolalkane(C11)PEG6-OH (11-mercaptoundecyl) hexaethyleneglycol, (SPT-0011P6, SensoPath Technologies, Inc., Bozeman, MT)[23]. Grids were incubated with this self-assembled, monolayer (SAM) solution for 24 hours. Prior to grid freezing, grids were removed from the SAM solution and rinsed with EtOH. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: LEICA EM GP / Details: blot for 3.5s before plunging. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 10926 / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |