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Yorodumi- EMDB-45412: Cryo-EM Structure of the Human Neutralizing Antibody 5-1 in Compl... -
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Basic information
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| Title | Cryo-EM Structure of the Human Neutralizing Antibody 5-1 in Complex with Prefusion Human Metapneumovirus F Glycoprotein | |||||||||
Map data | unsharpend EM Map | |||||||||
Sample |
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Keywords | hMPV F / 5-1 antibody / antibody / VIRAL PROTEIN-IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
| Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane / virion membrane / Fusion glycoprotein F0 Function and homology information | |||||||||
| Biological species | human metapneumovirus / Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 4.24 Å | |||||||||
Authors | Guo LQ / McLellan JS | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Cell Rep Med / Year: 2026Title: A potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein. Authors: Alexandra A Abu-Shmais / Luqiang Guo / Ahmed Magdy Khalil / Sabina E Leonard / Rose J Miller / Alexis K Janke / Matthew J Vukovich / Lindsay E Bass / Yukthi P Suresh / Scott A Rush / Rachael ...Authors: Alexandra A Abu-Shmais / Luqiang Guo / Ahmed Magdy Khalil / Sabina E Leonard / Rose J Miller / Alexis K Janke / Matthew J Vukovich / Lindsay E Bass / Yukthi P Suresh / Scott A Rush / Rachael M Wolters / Nurgun Kose / Robert H Carnahan / James E Crowe / Rachel H Bonami / Jarrod J Mousa / Jason S McLellan / Ivelin S Georgiev / ![]() Abstract: Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations. The primary target of neutralizing antibodies is ...Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations. The primary target of neutralizing antibodies is the fusion (F) glycoprotein on the surface of the RSV and hMPV virion. As a result of the structural conservation between RSV and hMPV F, three antigenic regions are known to induce cross-neutralizing responses: sites III, IV, and V. Leveraging LIBRA-seq, we identify five RSV/hMPV cross-reactive human antibodies. One antibody, RM 5-1, potently neutralizes all tested viruses from the major subgroups of RSV and hMPV and provides protection against RSV and hMPV in a mouse challenge model. Structural analysis reveals that RM 5-1 utilizes an uncommon genetic signature to bind an epitope that spans sites Ø, II, and V. These findings highlight the molecular and structural elements influencing RSV and hMPV cross-reactivity as well as the potential of antibody RM 5-1 for translational development. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_45412.map.gz | 88 MB | EMDB map data format | |
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| Header (meta data) | emd-45412-v30.xml emd-45412.xml | 26.5 KB 26.5 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_45412_fsc.xml | 16.6 KB | Display | FSC data file |
| Images | emd_45412.png | 51.1 KB | ||
| Masks | emd_45412_msk_1.map | 178 MB | Mask map | |
| Filedesc metadata | emd-45412.cif.gz | 7.2 KB | ||
| Others | emd_45412_additional_1.map.gz emd_45412_half_map_1.map.gz emd_45412_half_map_2.map.gz | 160.2 MB 165.2 MB 165.2 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-45412 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-45412 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9cb1MC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_45412.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | unsharpend EM Map | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| 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
-Mask #1
| File | emd_45412_msk_1.map | ||||||||||||
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-Additional map: Sharpened EM map by DeepEMhancer
| File | emd_45412_additional_1.map | ||||||||||||
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| Annotation | Sharpened EM map by DeepEMhancer | ||||||||||||
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-Half map: #1
| File | emd_45412_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_45412_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : The protein complex of hMPV F-DsCavEs2-IPDS and 5-1 Fab
| Entire | Name: The protein complex of hMPV F-DsCavEs2-IPDS and 5-1 Fab |
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| Components |
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-Supramolecule #1: The protein complex of hMPV F-DsCavEs2-IPDS and 5-1 Fab
| Supramolecule | Name: The protein complex of hMPV F-DsCavEs2-IPDS and 5-1 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: hMPV F-DsCavEs2-IPDS Trimer
| Supramolecule | Name: hMPV F-DsCavEs2-IPDS Trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #3 |
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| Source (natural) | Organism: human metapneumovirus |
-Supramolecule #3: 5-1 Fab Heavy chain Variable Domain
| Supramolecule | Name: 5-1 Fab Heavy chain Variable Domain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: 5-1 Fab Light Chain Variable Domain
| Supramolecule | Name: 5-1 Fab Light Chain Variable Domain / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #2 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: 5-1 Fab Heavy Chain Variable Domain
| Macromolecule | Name: 5-1 Fab Heavy Chain Variable Domain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 23.170996 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QGQLVQSGPE VKKPGATVKV SCRASAYPFG NYGITWVRQV PGQGLEWVGW ISAYTGHTKF PQNFQGRVTL TADTSTSTGY MELRSLTSD DTAVYYCARG PCCSSPRPYD IWGQGTMVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QGQLVQSGPE VKKPGATVKV SCRASAYPFG NYGITWVRQV PGQGLEWVGW ISAYTGHTKF PQNFQGRVTL TADTSTSTGY MELRSLTSD DTAVYYCARG PCCSSPRPYD IWGQGTMVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK V |
-Macromolecule #2: 5-1 Fab Light Chain Variable Domain
| Macromolecule | Name: 5-1 Fab Light Chain Variable Domain / 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: 23.586084 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: DIQMTQSPST LSASVGDRVT ITCRASQSID DWLAWYQHSP GKAPKLLIYR ASRLESGVPS RFSGSGSGTE FTLTISSLQP DDFASYYCQ QCYTYSQTFG QGTRVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPST LSASVGDRVT ITCRASQSID DWLAWYQHSP GKAPKLLIYR ASRLESGVPS RFSGSGSGTE FTLTISSLQP DDFASYYCQ QCYTYSQTFG QGTRVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #3: Fusion glycoprotein F0
| Macromolecule | Name: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: human metapneumovirus |
| Molecular weight | Theoretical: 60.48993 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MSWKVVIIFS LLITPQHGLK ESYLEESCST ITEGYLSVLR TGWYTNVFTL EVGDVENLTC ADGPSLIKTE LDLTKSALRE LRTCSADQL AREEQIENPR RRRFVLGAIA CGVATAAAVT AGVAIAKCIR LESEVTAIKN CLKKTNECVS TLGCGVRVLA T AVRELKDF ...String: MSWKVVIIFS LLITPQHGLK ESYLEESCST ITEGYLSVLR TGWYTNVFTL EVGDVENLTC ADGPSLIKTE LDLTKSALRE LRTCSADQL AREEQIENPR RRRFVLGAIA CGVATAAAVT AGVAIAKCIR LESEVTAIKN CLKKTNECVS TLGCGVRVLA T AVRELKDF VSKNLTRAIN KNKCDIPDLK MAVSFSQFNR RFLNVVRQFS DNAGITPAIS KDLMTDAELA RAISNMPTSA GQ IKLMLEN RCMVRRKGFG 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 UniProtKB: Fusion glycoprotein F0 |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 / Details: PBS, pH 7.4 |
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| Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
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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) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Average exposure time: 13.2 sec. / Average electron dose: 48.64 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 150000 |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
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About Yorodumi



Keywords
human metapneumovirus
Homo sapiens (human)
Authors
United States, 1 items
Citation


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Processing
FIELD EMISSION GUN
