[English] 日本語
Yorodumi- EMDB-41179: HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41179 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | |||||||||
Map data | Composite map for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | |||||||||
Sample |
| |||||||||
Keywords | Virus / glycoprotein / antibody / VIRAL PROTEIN | |||||||||
Function / homology | Herpesvirus UL130, cytomegalovirus / HCMV glycoprotein pUL130 / viral envelope / Envelope glycoprotein UL130 / UL128 / UL131A Function and homology information | |||||||||
Biological species | Human betaherpesvirus 5 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Goldsmith JA / McLellan JS | |||||||||
Funding support | 1 items
| |||||||||
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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_41179.map.gz | 190 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-41179-v30.xml emd-41179.xml | 17.5 KB 17.5 KB | Display Display | EMDB header |
Images | emd_41179.png | 49.1 KB | ||
Filedesc metadata | emd-41179.cif.gz | 6.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41179 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41179 | HTTPS FTP |
-Validation report
Summary document | emd_41179_validation.pdf.gz | 312.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_41179_full_validation.pdf.gz | 311.8 KB | Display | |
Data in XML | emd_41179_validation.xml.gz | 7.1 KB | Display | |
Data in CIF | emd_41179_validation.cif.gz | 8.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41179 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41179 | HTTPS FTP |
-Related structure data
Related structure data | 8teaMC 8tcoC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|
-Map
File | Download / File: emd_41179.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Composite map for HCMV Pentamer in complex with CS2pt1p2_A10L Fab and CS3pt1p4_C1L Fab | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.94 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-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 |
---|---|
Components |
|
-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 / Macromolecule list: #1-#3, #7, #5-#6, #4 |
---|---|
Source (natural) | Organism: Human betaherpesvirus 5 |
-Macromolecule #1: Envelope protein UL128
Macromolecule | Name: Envelope protein UL128 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Human betaherpesvirus 5 |
Molecular weight | Theoretical: 18.940904 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEWSWVFLFF LSVTTGVHSE ECCEFINVNH PPERCYDFKM CNRFTVALRC PDGEVCYSPE KTAEIRGIVT TMTHSLTRQV VHNKLTSCN YNPLYLEADG RIRCGKVNDK AQYLLGAAGS VPYRWINLEY DKITRIVGLD QYLESVKKHK RLDVCRAKMG Y MLQ UniProtKB: UL128 |
-Macromolecule #2: Envelope glycoprotein UL130
Macromolecule | Name: Envelope glycoprotein UL130 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Human betaherpesvirus 5 |
Molecular weight | Theoretical: 24.018285 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEWSWVFLFF LSVTTGVHSS PWSTLTANQN PSPPWSKLTY SKPHDAATFY CPFLYPSPPR SPLQFSGFQQ VSTGPECRNE TLYLLYNRE GQTLVERSST WVKKVIWYLS GRNQTILQRM PQTASKPSDG NVQISVEDAK IFGAHMVPKQ TKLLRFVVND G TRYQMCVM ...String: MEWSWVFLFF LSVTTGVHSS PWSTLTANQN PSPPWSKLTY SKPHDAATFY CPFLYPSPPR SPLQFSGFQQ VSTGPECRNE TLYLLYNRE GQTLVERSST WVKKVIWYLS GRNQTILQRM PQTASKPSDG NVQISVEDAK IFGAHMVPKQ TKLLRFVVND G TRYQMCVM KLESWAHVFR DYSVSFQVRL TFTEANNQTY TFCTHPNLIV UniProtKB: Envelope glycoprotein UL130 |
-Macromolecule #3: UL131A
Macromolecule | Name: UL131A / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Human betaherpesvirus 5 |
Molecular weight | Theoretical: 15.262057 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEWSWVFLFF LSVTTGVHSQ CQRETAEKND YYRVPHYWDA CSRALPDQTR YKYVEQLVDL TLNYHYDASH GLDNFDVLKR INVTEVSLL ISDFRRQNRR GGTNKRTTFN AAGSLAPHAR SLEFSVRLFA N UniProtKB: UL131A |
-Macromolecule #4: CS2pt1p2_A10L Fab light chain
Macromolecule | Name: CS2pt1p2_A10L Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.850111 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSALTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVHWYQQL PGTAPKLLIY SNNQRPSGVP DRFSGSRSGT SASLAISGLR SEDEADYYC AAWDDSLNGR VFGTGTKVTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String: QSALTQPPSA SGTPGQRVTI SCSGSSSNIG SNTVHWYQQL PGTAPKLLIY SNNQRPSGVP DRFSGSRSGT SASLAISGLR SEDEADYYC AAWDDSLNGR VFGTGTKVTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS |
-Macromolecule #5: CS2pt1p2_A10L Fab heavy chain
Macromolecule | Name: CS2pt1p2_A10L Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.916252 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEFGLSWVFL VALIKGVQCQ VHLEESGGGL VKPGGSLRLS CVASGFSFSD YYMSWIRQAP GKGLEWLSYI SPSGSPTSNA DSMKGRFTI SRDNARSSLY LQVHSLRVED TAVYYCARDN TVFGVVTTPM DHWGQGTLVT VSSASTKGPS VFPLAPSSKS T SGGTAALG ...String: MEFGLSWVFL VALIKGVQCQ VHLEESGGGL VKPGGSLRLS CVASGFSFSD YYMSWIRQAP GKGLEWLSYI SPSGSPTSNA DSMKGRFTI SRDNARSSLY LQVHSLRVED TAVYYCARDN TVFGVVTTPM DHWGQGTLVT VSSASTKGPS VFPLAPSSKS T SGGTAALG CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RV EPK |
-Macromolecule #6: CS3pt1p4_C1L Fab heavy chain
Macromolecule | Name: CS3pt1p4_C1L Fab heavy chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.630592 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFT DYALSWVRQA PGQGLEWMGG IIPVLGTPHY AQKFEDRVTI IADESTGTVF MALSSLRSD DTGMYYCARG VTHPYYYYAM DVWGQGTTIT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFT DYALSWVRQA PGQGLEWMGG IIPVLGTPHY AQKFEDRVTI IADESTGTVF MALSSLRSD DTGMYYCARG VTHPYYYYAM DVWGQGTTIT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK RVEPK |
-Macromolecule #7: CS3pt1p4_C1L Fab light chain
Macromolecule | Name: CS3pt1p4_C1L Fab light chain / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.239676 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSALTQPASV SGSPGQSISI SCTGTSSDVG AYDYVSWYQQ HPGKAPRLII YDVNKRPSGV PYRFSGSKSG TAASLTISGL QSEDEAVYY CGSYTSSSAF FYVFGTGTMV TVLRQPKANP TVTLFPPSSE ELQANKATLV CLISDFYPGA VTVAWKADSS P VKAGVETT ...String: QSALTQPASV SGSPGQSISI SCTGTSSDVG AYDYVSWYQQ HPGKAPRLII YDVNKRPSGV PYRFSGSKSG TAASLTISGL QSEDEAVYY CGSYTSSSAF FYVFGTGTMV TVLRQPKANP TVTLFPPSSE ELQANKATLV CLISDFYPGA VTVAWKADSS P VKAGVETT TPSKQSNNKY AASSYLSLTP EQWKSHRSYS CQVTHEGSTV EKTVAPTECS |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
---|---|
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: |
---|---|
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 |