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- EMDB-41156: HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab | |||||||||
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![]() | Virus / glycoprotein / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() host cell endosome membrane / host cell Golgi apparatus / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Goldsmith JA / McLellan JS | |||||||||
Funding support | 1 items
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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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 131.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.6 KB 17.6 KB | Display Display | ![]() |
Images | ![]() | 47.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8tcoMC ![]() 8teaC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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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
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Sample components
-Entire : HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab
Entire | Name: HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab |
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Components |
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-Supramolecule #1: HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab
Supramolecule | Name: HCMV Trimer in complex with CS2it1p2_F7K Fab and CS4tt1p1_E3K Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Envelope glycoprotein H
Macromolecule | Name: Envelope glycoprotein H / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 84.538617 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRPGLPPYLT VFTVYLLSHL PSQRYGADAA SEALDPHAFH LLLNTYGRPI RFLRENTTQC TYNSSLRNST VVRENAISFN FFQSYNQYY VFHMPRCLFA GPLAEQFLNQ VDLTETLERY QQRLNTYALV SKDLASYRSF SQQLKAQDSL GQQPTTVPPP I DLSIPHVW ...String: MRPGLPPYLT VFTVYLLSHL PSQRYGADAA SEALDPHAFH LLLNTYGRPI RFLRENTTQC TYNSSLRNST VVRENAISFN FFQSYNQYY VFHMPRCLFA GPLAEQFLNQ VDLTETLERY QQRLNTYALV SKDLASYRSF SQQLKAQDSL GQQPTTVPPP I DLSIPHVW MPPQTTPHDW KGSHTTSGLH RPHFNQTCIL FDGHDLLFST VTPCLHQGFY LMDELRYVKI TLTEDFFVVT VS IDDDTPM LLIFGHLPRV LFKAPYQRDN FILRQTEKHE LLVLVKKAQL NRHSYLKDSD FLDAALDFNY LDLSALLRNS FHR YAVDVL KSGRCQMLDR RTVEMAFAYA LALFAAARQE EAGTEISIPR ALDRQAALLQ IQEFMITCLS QTPPRTTLLL YPTA VDLAK RALWTPDQIT DITSLVRLVY ILSKQNQQHL IPQWALRQIA DFALQLHKTH LASFLSAFAR QELYLMGSLV HSMLV HTTE RREIFIVETG LCSLAELSHF TQLLAHPHHE YLSDLYTPCS SSGRRDHSLE RLTRLFPDAT VPATVPAALS ILSTMQ PST LETFPDLFCL PLGESFSALT VSEHVSYVVT NQYLIKGISY PVSTTVVGQS LIITQTDSQT KCELTRNMHT THSITAA LN ISLENCAFCQ SALLEYDDTQ GVINIMYMHD SDDVLFALDP YNEVVVSSPR THYLMLLKNG TVLEVTDVVV DATDSRLL M MSVYALSAII GIYLLYRMLK TC UniProtKB: Envelope glycoprotein H |
-Macromolecule #2: Envelope glycoprotein L
Macromolecule | Name: Envelope glycoprotein L / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 29.877336 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSVPTQVLGL LLLWLTDARC VAVSVAPTAA EKVPAECPEL TRRCLLGEVF QGDKYESWLR PLVNVTRRDG PLSQLIRYRP VTPEAANSV LLDDAFLDTL ALLYNNPDQL RALLTLLSSD TAPRWMTVMR GYSECGDGSP AVYTCVDDLC RGYDLTRLSY G RSIFTEHV ...String: MSVPTQVLGL LLLWLTDARC VAVSVAPTAA EKVPAECPEL TRRCLLGEVF QGDKYESWLR PLVNVTRRDG PLSQLIRYRP VTPEAANSV LLDDAFLDTL ALLYNNPDQL RALLTLLSSD TAPRWMTVMR GYSECGDGSP AVYTCVDDLC RGYDLTRLSY G RSIFTEHV LGFELVPPSL FNVVVAIRNE ATRTNRAVRL PVSTAAAPEG ITLFYGLYNA VKEFCLRHQL DPPLLRHLDK YY AGLPPEL KQTRVNLPAH SRYGPQAVDA R UniProtKB: Envelope glycoprotein L |
-Macromolecule #3: Envelope glycoprotein O
Macromolecule | Name: Envelope glycoprotein O / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 54.299551 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGRKEMMVRD VPKMVFLISI SFLLVSFINC KVMSKALYNR PWRGLVLSKI GKYKLDQLKL EILRQLETTI STKYNVSKQP VKNLTMNMT EFPQYYILAG PIQNYSITYL WFDFYSTQLR KPAKYVYSQY NHTAKTITFR PPPCGTVPSM TCLSEMLNVS K RNDTGEQG ...String: MGRKEMMVRD VPKMVFLISI SFLLVSFINC KVMSKALYNR PWRGLVLSKI GKYKLDQLKL EILRQLETTI STKYNVSKQP VKNLTMNMT EFPQYYILAG PIQNYSITYL WFDFYSTQLR KPAKYVYSQY NHTAKTITFR PPPCGTVPSM TCLSEMLNVS K RNDTGEQG CGNFTTFNPM FFNVPRWNTK LYVGPTKVNV DSQTIYFLGL TALLLRYAQR NCTHSFYLVN AMSRNLFRVP KY INGTKLK NTMRKLKRKQ APVKEQFEKK AKKTQSTTTP YFSYTTSAAL NVTTNVTYSI TTAARRVSTS TIAYRPDSSF MKS IMATQL RDLATWVYTT LRYRQNPFCE PSRNRTAVSE FMKNTHVLIR NETPYTIYGT LDMSSLYYNE TMFVENKTAS DSNK TTPTS PSMGFQRTFI DPLWDYLDSL LFLDEIRNFS LRSPTYVNLT PPEHRRAVNL STLNSLWWWL Q UniProtKB: Envelope glycoprotein O |
-Macromolecule #4: CS4tt1p1_E3K Fab light chain
Macromolecule | Name: CS4tt1p1_E3K Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.793338 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQLTQSPSS LSASVGDRVT ITCRASQNIY NWLAWYQQKP GQAPKLLIFD ASTLEGGVPS RFGGSGSGTD FTLTISNLRP EDFATYFCQ HYYNYPPWTF GQGTKVTFRR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: DIQLTQSPSS LSASVGDRVT ITCRASQNIY NWLAWYQQKP GQAPKLLIFD ASTLEGGVPS RFGGSGSGTD FTLTISNLRP EDFATYFCQ HYYNYPPWTF GQGTKVTFRR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #5: CS4tt1p1_E3K Fab heavy chain
Macromolecule | Name: CS4tt1p1_E3K Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.053139 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVRLVESGGG FVQTGGSLRL SCAASGYTFD QYSMHWVRQV PGKGLQFVST ISSNGGSRYY ADSVKGRFVV SRDEEKEVLY LQMGRLRTD DTGIYFCARA KKIFGGIIPP SGMDVWGRGT TVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: EVRLVESGGG FVQTGGSLRL SCAASGYTFD QYSMHWVRQV PGKGLQFVST ISSNGGSRYY ADSVKGRFVV SRDEEKEVLY LQMGRLRTD DTGIYFCARA KKIFGGIIPP SGMDVWGRGT TVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKRVEPK |
-Macromolecule #6: CS2it1p2_F7K Fab heavy chain
Macromolecule | Name: CS2it1p2_F7K Fab heavy chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.41534 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGASVRV SCKVSGYTLT DLSIHWVRQA PGKGLEWMGG FDPEHGEIMY AQKFQGRVTV TEDTSTHTTY MEVNSLRSE DTAVYYCATD SSIAMTGTYF SDLFALDVWG QGTTVIVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVQLVQSGAE VKKPGASVRV SCKVSGYTLT DLSIHWVRQA PGKGLEWMGG FDPEHGEIMY AQKFQGRVTV TEDTSTHTTY MEVNSLRSE DTAVYYCATD SSIAMTGTYF SDLFALDVWG QGTTVIVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKRVEP K |
-Macromolecule #7: CS2it1p2_F7K Fab light chain
Macromolecule | Name: CS2it1p2_F7K Fab light chain / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.607836 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRLPAQLLGL LLLWLRGARC DIQMTQSPSS LSASVGDRVT ITCRASQTIN TNLNWYQQKP GKAPRLLIFG TFSLKSGVPS RFSGGGSGT DFTLTISSLQ PEDFAAYFCQ QSHSPPHTFG QGTKLELKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW ...String: MRLPAQLLGL LLLWLRGARC DIQMTQSPSS LSASVGDRVT ITCRASQTIN TNLNWYQQKP GKAPRLLIFG TFSLKSGVPS RFSGGGSGT DFTLTISSLQ PEDFAAYFCQ QSHSPPHTFG QGTKLELKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF Y PREAKVQW KVDNALQSGN SQESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 7 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 376687 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |