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Yorodumi- EMDB-27024: Prefusion-stabilized hMPV fusion protein bound to ADI-61026 and M... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27024 | |||||||||
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Title | Prefusion-stabilized hMPV fusion protein bound to ADI-61026 and MPE8 Fabs | |||||||||
Map data | CompositeMap | |||||||||
Sample |
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Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | |||||||||
Biological species | Human metapneumovirus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.46 Å | |||||||||
Authors | Hsieh C-L / McLellan JS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Immunity / Year: 2022 Title: Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein. Authors: C Garrett Rappazzo / Ching-Lin Hsieh / Scott A Rush / Emma S Esterman / Teresa Delgado / James C Geoghegan / Anna Z Wec / Mrunal Sakharkar / Vicente Más / Jason S McLellan / Laura M Walker / Abstract: Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or ...Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27024.map.gz | 50.4 MB | EMDB map data format | |
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Header (meta data) | emd-27024-v30.xml emd-27024.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
Images | emd_27024.png | 101.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27024 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27024 | HTTPS FTP |
-Validation report
Summary document | emd_27024_validation.pdf.gz | 321.7 KB | Display | EMDB validaton report |
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Full document | emd_27024_full_validation.pdf.gz | 321.3 KB | Display | |
Data in XML | emd_27024_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_27024_validation.cif.gz | 7.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27024 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27024 | HTTPS FTP |
-Related structure data
Related structure data | 8cw9MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_27024.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | CompositeMap | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.36688 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : hMPV fusion protein bound to ADI-61026 and MPE8 Fabs
Entire | Name: hMPV fusion protein bound to ADI-61026 and MPE8 Fabs |
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Components |
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-Supramolecule #1: hMPV fusion protein bound to ADI-61026 and MPE8 Fabs
Supramolecule | Name: hMPV fusion protein bound to ADI-61026 and MPE8 Fabs / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: Human metapneumovirus |
-Macromolecule #1: Fusion glycoprotein F0
Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human metapneumovirus |
Molecular weight | Theoretical: 60.453852 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSWKVVIIFS LLITPQHGLK ESYLEESCST ITEGYLSVLR TGWYTNVFTL EVGDVENLTC ADGPSLIKTE LDLTKSALRE LRTVSADQL AREEQIENPR RRRFVLGAIA CGVATAAAVT AGVAIAKCIR LESEVTAIKN CLKKTNECVS TLGCGVRVLA T AVRELKDF ...String: MSWKVVIIFS LLITPQHGLK ESYLEESCST ITEGYLSVLR TGWYTNVFTL EVGDVENLTC ADGPSLIKTE LDLTKSALRE LRTVSADQL AREEQIENPR RRRFVLGAIA CGVATAAAVT AGVAIAKCIR LESEVTAIKN CLKKTNECVS TLGCGVRVLA T AVRELKDF VSKNLTRAIN KNKCDIPDLK MAVSFSQFNR RFLNVVRQFS DNAGITPAIS KDLMTDAELA RAISNMPTSA GQ IKLMLEN RAMVRRKGFG ILIGVYGSSV IYMVQLPIFG VIDTPCWIVK AAPSCSEKKG NYACLLREDQ GWYCQNAGST VYY PCEKDC ETRGDHVFCD TAAGINVAEQ SKECNINIST TNYPCKVSCG RHPISMVALS PLGALVACYK GVSCSIGSNR VGII KQLNK GCSYITNQDA DTVTIDNTVY QLSKVEGEQH VIKGRPVSSS FDPVKFPQDQ FNVALDQCFE SIENSQALVD QSNRI LSSA EKGNTGGGGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGRS LEVLFQGPGH HHHHHHHSAW SHPQFEK |
-Macromolecule #2: MPE8 light chain
Macromolecule | Name: MPE8 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.772092 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QSVVTQPPSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YDNNNRPSGV PDRFSASKSG TSASLAITGL QAEDEADYY CQSYDRSLSG VFGTGTKVTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String: QSVVTQPPSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YDNNNRPSGV PDRFSASKSG TSASLAITGL QAEDEADYY CQSYDRSLSG VFGTGTKVTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHKSYSCQ VTHEGSTVEK TVAPTECS |
-Macromolecule #3: ADI-61026 heavy
Macromolecule | Name: ADI-61026 heavy / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.699928 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGPA LVKSTQTLTL TCTFSGFALT TSGMCVSWVR QPPGKALEWL ARIDWEDNTY YSTSLKTRVT ISKDPSKNQV VLTMTNMDP VDTATYYCAR SYITDWKKDW FFDLWGRGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: QVQLVQSGPA LVKSTQTLTL TCTFSGFALT TSGMCVSWVR QPPGKALEWL ARIDWEDNTY YSTSLKTRVT ISKDPSKNQV VLTMTNMDP VDTATYYCAR SYITDWKKDW FFDLWGRGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD |
-Macromolecule #4: ADI-61026 light
Macromolecule | Name: ADI-61026 light / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.912414 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SYELIQLPSV SVSPGQTARI PCSGDGLPKK YAHWYQQKAG QAPILLMYKD SERPSGIPER FSAFSSGTTV TMTISGVQEE DEADYYCQS GDSTDTSVIF GGGTKVTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String: SYELIQLPSV SVSPGQTARI PCSGDGLPKK YAHWYQQKAG QAPILLMYKD SERPSGIPER FSAFSSGTTV TMTISGVQEE DEADYYCQS GDSTDTSVIF GGGTKVTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS |
-Macromolecule #5: MPE8 heavy chain
Macromolecule | Name: MPE8 heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.433516 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVKPGGSLRL SCAASGFTFS SYSMNWVRQA PGKGLEWVSS ISASSSYSDY ADSAKGRFTI SRDNAKTSLF LQMNSLRAE DTAIYFCARA RATGYSSITP YFDIWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: EVQLVESGGG LVKPGGSLRL SCAASGFTFS SYSMNWVRQA PGKGLEWVSS ISASSSYSDY ADSAKGRFTI SRDNAKTSLF LQMNSLRAE DTAIYFCARA RATGYSSITP YFDIWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PE LLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDW LNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKT TPPVL DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGK |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 3 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.36 mg/mL |
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Buffer | pH: 8 Details: 2 mM Tris pH 8.0, 200 mM NaCl, 0.02% NaN3, 0.075% amphipol |
Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Mesh: 400 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 30 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K |
Details | 0.36 mg/mL hMPV F (2 mM Tris pH 8.0, 200 mM NaCl, 0.02% NaN3, 0.075% amphipol) and 2-folds molar excess MPE8 and 1.5- folds molar excess ADI-61026 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.46 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 113336 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |