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- EMDB-25688: CryoEM structure of 2x 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 2x HCMV Pentamer gH/gL/UL128/UL130/UL131A in complex with NRP2 and 2x neutralizing fabs 8I21 and 13H11 | |||||||||
![]() | Full map of overall pentamer-NRP2-dimer | |||||||||
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![]() | Human Cytomegalovirus / glycoprotein complex / antibody complex / Neuropilin 2 / VIRAL PROTEIN | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.84 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 | ![]() | 226.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 34.4 KB 34.4 KB | Display Display | ![]() |
Images | ![]() | 83.8 KB | ||
Filedesc metadata | ![]() | 8 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() | 149.2 MB 226.2 MB 149.2 MB 149 MB 149 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | Full map of overall pentamer-NRP2-dimer | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0712 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Half map 1 of focused refinement on NRP2-UL region
File | emd_25688_additional_1.map | ||||||||||||
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Annotation | Half map 1 of focused refinement on NRP2-UL region | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Full map of focused refinement on NRP2-UL region
File | emd_25688_additional_2.map | ||||||||||||
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Annotation | Full map of focused refinement on NRP2-UL region | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Half map 2 of focused refinement on NRP2-UL region
File | emd_25688_additional_3.map | ||||||||||||
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Annotation | Half map 2 of focused refinement on NRP2-UL region | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 of overall pentamer-NRP2-dimer
File | emd_25688_half_map_1.map | ||||||||||||
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Annotation | Half map 2 of overall pentamer-NRP2-dimer | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1 of overall pentamer-NRP2-dimer
File | emd_25688_half_map_2.map | ||||||||||||
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Annotation | Half map 1 of overall pentamer-NRP2-dimer | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Complex of 2x HCMV Pentamer proteins gH, gL, UL128, UL130, UL131A...
+Supramolecule #1: Complex of 2x HCMV Pentamer proteins gH, gL, UL128, UL130, UL131A...
+Macromolecule #1: HCMV envelope glycoprotein H
+Macromolecule #2: HCMV envelope glycoprotein L
+Macromolecule #3: HCMV envelope glycoprotein UL128
+Macromolecule #4: HCMV envelope glycoprotein UL130
+Macromolecule #5: HCMV envelope glycoprotein UL131A
+Macromolecule #6: Neuropilin-2
+Macromolecule #7: Fab 8I21 heavy chain
+Macromolecule #8: Fab 8I21 light chain
+Macromolecule #9: Fab 13H11 heavy chain
+Macromolecule #10: Fab 13H11 light chain
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: LEICA EM GP / Details: blot for 3.5 seconds before plunging. | |||||||||
Details | Sample was mildly crosslinked with 0.025% glutaraldehyde, incubated for 10 min at room temperature and quenched with 9 mM TRIS pH 7.5 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 4 / Number real images: 21357 / Average exposure time: 10.0 sec. / Average electron dose: 52.0 e/Å2 Details: Images were collected in movie-mode at 4 frames/second. |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm / 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 |