+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27990 | |||||||||
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Title | HMPV F complex with 4I3 Fab | |||||||||
Map data | ||||||||||
Sample |
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Keywords | human antibodies / RSV and MPV Fusion protein / complex Cryo-EM structure / viral protein and antiviral protein / BIOSYNTHETIC PROTEIN | |||||||||
Biological species | Human metapneumovirus / Human metapneumovirus A / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / Resolution: 3.33 Å | |||||||||
Authors | Wen X / Jardetzky TS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Host Microbe / Year: 2023 Title: Potent cross-neutralization of respiratory syncytial virus and human metapneumovirus through a structurally conserved antibody recognition mode. Authors: Xiaolin Wen / Naveenchandra Suryadevara / Nurgun Kose / Jing Liu / Xiaoyan Zhan / Laura S Handal / Lauren E Williamson / Andrew Trivette / Robert H Carnahan / Theodore S Jardetzky / James E Crowe / Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F ...Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27990.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-27990-v30.xml emd-27990.xml | 17.8 KB 17.8 KB | Display Display | EMDB header |
Images | emd_27990.png | 18.7 KB | ||
Others | emd_27990_half_map_1.map.gz emd_27990_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27990 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27990 | HTTPS FTP |
-Related structure data
Related structure data | 8eayMC 8dzwC 8e2uC 8ebpC C: citing same article (ref.) M: atomic model generated by this map |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_27990.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_27990_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_27990_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : MPV fusion protein complex with 4I3 Fab
Entire | Name: MPV fusion protein complex with 4I3 Fab |
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Components |
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-Supramolecule #1: MPV fusion protein complex with 4I3 Fab
Supramolecule | Name: MPV fusion protein complex with 4I3 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human metapneumovirus A |
Molecular weight | Theoretical: 45.044461 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: LKESYLEESC STITEGYLSV LRTGWYTNVF TLEVGDVENL TCADGPSLIK TELDLTKSAL RELRTVSADQ LAREEQIENP RQSRFVLGA IALGVCTAAA VTAGVAIAKT IRLESEVTAI KNALKKTNEA VSTLGNGVRV LATAVRELKD FVSKNLTRAI N KNKCDIPD ...String: LKESYLEESC STITEGYLSV LRTGWYTNVF TLEVGDVENL TCADGPSLIK TELDLTKSAL RELRTVSADQ LAREEQIENP RQSRFVLGA IALGVCTAAA VTAGVAIAKT IRLESEVTAI KNALKKTNEA VSTLGNGVRV LATAVRELKD FVSKNLTRAI N KNKCDIPD LKMAVSFSQF NRRFLNVVRQ FSDNAGITPA ISLDLMTDAE LARAVSNMPT SAGQIKLMLE NRAMVRRKGF GI LIGVYGS SVIYMVQLPI FGVIDTPCWI VKAAPSCSEK KGNYACLLRE DQGWYCQNAG STVYYPNEKD CETRGDHVFC DTA CGINVA EQSKECNINI STTNYPCKVS TGRHPISMVA LSPLGALVAC YKGVSCSIGS NRVGIIKQLN KGCSYITNQD ADTV TIDNT VYQLSKVEG |
-Macromolecule #2: 4I3 heavy chain protein
Macromolecule | Name: 4I3 heavy chain protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.376045 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLQESGPG LVKPSETLSL TCTVSGGSIS NYYWNWIRQP PGKGLEWIGY FYYSGSTKYN PSLKSRVTIS LDMSKNQFSL KLRSVTAAD TAVYYCARGT MRESGMPDAF DIWGQGTVVT VS |
-Macromolecule #3: 4I3 light chain protein
Macromolecule | Name: 4I3 light chain protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.438607 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SYELIQPPSV SVSPGQTAII TCSGNNLGNK YACWYQQKAG QSPVMIIYQD NRRPSGIPER FSGSNSGNTA TLTISGTQAM DEADYYCQA WDSSVVFGGG TKLTVLGQ |
-Experimental details
-Structure determination
Processing | single particle reconstruction |
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Aggregation state | particle |
-Sample preparation
Concentration | 1.8 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 36.522 µm / Nominal defocus min: 11.445 µm / Nominal magnification: 81000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |