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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | HMPV F dimer bound to RSV-199 Fab | |||||||||
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Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() | |||||||||
![]() | Wen X / Jardetzky TS | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 33.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.8 KB 18.8 KB | Display Display | ![]() |
Images | ![]() | 39.5 KB | ||
Others | ![]() ![]() ![]() | 117.9 MB 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ebpMC ![]() 8dzwC ![]() 8e2uC ![]() 8eayC M: atomic model generated by this map C: citing same article ( |
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Links
EMDB pages | ![]() ![]() |
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Map
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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
-Additional map: #1
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Density Histograms |
-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : MPV fusion protein complex with RSV-199 Fab
Entire | Name: MPV fusion protein complex with RSV-199 Fab |
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Components |
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-Supramolecule #1: MPV fusion protein complex with RSV-199 Fab
Supramolecule | Name: MPV fusion protein complex with RSV-199 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Fusion glycoprotein F0
Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 47.513301 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: LKESYLEESC STITEGYLSV LRTGWYTNVF TLEVGDVENL TCADGPSLIK TELDLTKSAL RELRTVSADQ LAREEQIENP RRRRFVLGA IALGVCTAAA VTAGVAIAKT IRLESEVTAI KNALKKTNEA VSTLGNGVRV LATAVRELKD FVSKNLTRAI N KNKCDIPD ...String: LKESYLEESC STITEGYLSV LRTGWYTNVF TLEVGDVENL TCADGPSLIK TELDLTKSAL RELRTVSADQ LAREEQIENP RRRRFVLGA 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 VYQLSKVEGE QHVIKGRPVS SSFDPVKFPE |
-Macromolecule #2: RSV-199 light chain protein
Macromolecule | Name: RSV-199 light chain protein / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.819264 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QAVVTQPPSV SGAPGQRVII SCTGSGSNLG ADYGVHWYQQ LPGTAPKLLI YGDRNRPSGV PDRFSGSKSG TSASLAITGL QAEDEADYY CQSYDRSLNW VFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV N AGVETTKP ...String: QAVVTQPPSV SGAPGQRVII SCTGSGSNLG ADYGVHWYQQ LPGTAPKLLI YGDRNRPSGV PDRFSGSKSG TSASLAITGL QAEDEADYY CQSYDRSLNW VFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV N AGVETTKP SKQSNNKYAA SSYLSLTPEQ WKSHKSYSCQ VTHEGSTVEK TVAPAECS |
-Macromolecule #3: RSV-199 heavy chain protein
Macromolecule | Name: RSV-199 heavy chain protein / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.022906 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLVESGGG VVKPGGSLRV SCVVSGFTFS SYRMHWVRQA PGKGLEWVSS ITASSSYINY AESVKGRFTI SRDNAKNSLY LQMNSLRAE DTAVYYCARD ENTGISHYWF DPWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QVQLVESGGG VVKPGGSLRV SCVVSGFTFS SYRMHWVRQA PGKGLEWVSS ITASSSYINY AESVKGRFTI SRDNAKNSLY LQMNSLRAE DTAVYYCARD ENTGISHYWF DPWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSC |
-Experimental details
-Structure determination
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Aggregation state | particle |
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Sample preparation
Concentration | 1.5 mg/mL |
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Buffer | pH: 7.5 |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 2774162 |
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Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
Initial angle assignment | Type: OTHER |
Final 3D classification | Number classes: 100 |
Final angle assignment | Type: OTHER |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 563257 |