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Yorodumi- EMDB-41180: Global reconstruction for HCMV Pentamer in complex with CS2pt1p2_... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41180 | |||||||||
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Title | Global reconstruction for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | |||||||||
Map data | Global reconstruction half map A for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | |||||||||
Sample |
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Keywords | Virus / glycoprotein / antibody / VIRAL PROTEIN | |||||||||
Biological species | Human betaherpesvirus 5 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Goldsmith JG / McLellan JS | |||||||||
Funding support | 1 items
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Citation | Journal: Immunity / Year: 2023 Title: Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer. Authors: Matthias Zehner / Mira Alt / Artem Ashurov / Jory A Goldsmith / Rebecca Spies / Nina Weiler / Justin Lerma / Lutz Gieselmann / Dagmar Stöhr / Henning Gruell / Eric P Schultz / Christoph ...Authors: Matthias Zehner / Mira Alt / Artem Ashurov / Jory A Goldsmith / Rebecca Spies / Nina Weiler / Justin Lerma / Lutz Gieselmann / Dagmar Stöhr / Henning Gruell / Eric P Schultz / Christoph Kreer / Linda Schlachter / Hanna Janicki / Kerstin Laib Sampaio / Cora Stegmann / Michelle D Nemetchek / Sabrina Dähling / Leon Ullrich / Ulf Dittmer / Oliver Witzke / Manuel Koch / Brent J Ryckman / Ramin Lotfi / Jason S McLellan / Adalbert Krawczyk / Christian Sinzger / Florian Klein / Abstract: Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we ...Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL and gO. Using high-resolution cryogenic electron microscopy, we revealed the structural basis of the neutralization mechanisms of antibodies targeting various binding sites. Moreover, we identified highly potent antibodies that neutralized a broad spectrum of HCMV strains, including primary clinical isolates, that outperform known antibodies used in clinical trials. Our study provides a deep understanding of the mechanisms of HCMV neutralization and identifies promising antibody candidates to prevent and treat HCMV infection. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41180.map.gz | 122.7 MB | EMDB map data format | |
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Header (meta data) | emd-41180-v30.xml emd-41180.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
Images | emd_41180.png | 41.1 KB | ||
Filedesc metadata | emd-41180.cif.gz | 4.1 KB | ||
Others | emd_41180_additional_1.map.gz emd_41180_half_map_1.map.gz emd_41180_half_map_2.map.gz | 214.6 MB 226.4 MB 226.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41180 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41180 | HTTPS FTP |
-Validation report
Summary document | emd_41180_validation.pdf.gz | 925.6 KB | Display | EMDB validaton report |
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Full document | emd_41180_full_validation.pdf.gz | 925.1 KB | Display | |
Data in XML | emd_41180_validation.xml.gz | 15.6 KB | Display | |
Data in CIF | emd_41180_validation.cif.gz | 18.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41180 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41180 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_41180.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Global reconstruction half map A for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Global reconstruction half sharpened map for HCMV Pentamer...
File | emd_41180_additional_1.map | ||||||||||||
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Annotation | Global reconstruction half sharpened map for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Global reconstruction map for HCMV Pentamer in complex...
File | emd_41180_half_map_1.map | ||||||||||||
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Annotation | Global reconstruction map for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Global reconstruction half map B for HCMV Pentamer...
File | emd_41180_half_map_2.map | ||||||||||||
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Annotation | Global reconstruction half map B for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab
Entire | Name: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab |
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Components |
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-Supramolecule #1: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab
Supramolecule | Name: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab type: complex / ID: 1 / Parent: 0 |
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-Supramolecule #2: HCMV Pentamer
Supramolecule | Name: HCMV Pentamer / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Human betaherpesvirus 5 |
-Supramolecule #3: CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab
Supramolecule | Name: CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab / 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 |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 49.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 71677 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |