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- PDB-8tea: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab -
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Open data
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Basic information
Entry | Database: PDB / ID: 8tea | ||||||
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Title | HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||
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![]() | VIRAL PROTEIN / Virus / glycoprotein / antibody | ||||||
Function / homology | Herpesvirus UL130, cytomegalovirus / HCMV glycoprotein pUL130 / viral envelope / Envelope glycoprotein UL130 / UL128 / UL131A![]() | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
![]() | Goldsmith, J.A. / McLellan, J.S. | ||||||
Funding support | 1items
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![]() | ![]() 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 211.7 KB | Display | ![]() |
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PDB format | ![]() | 129.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 41179MC ![]() 8tcoC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 3 types, 3 molecules CDE
#1: Protein | Mass: 18940.904 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 24018.285 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 15262.057 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody , 4 types, 4 molecules GHFI
#4: Antibody | Mass: 22850.111 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#5: Antibody | Mass: 25916.252 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#6: Antibody | Mass: 23630.592 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#7: Antibody | Mass: 23239.676 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab Type: COMPLEX / Entity ID: #1-#3, #7, #5-#6, #4 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 49 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71677 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 61.15 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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