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Yorodumi- EMDB-46994: Cryo-EM structure of the SFV009 3G01 Fab in complex with A/Califo... -
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Basic information
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| Title | Cryo-EM structure of the SFV009 3G01 Fab in complex with A/California/04/2009 | |||||||||
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Keywords | hemagglutinin / HA / antibody / anchor epitope / influenza virus / IMMUNE SYSTEM | |||||||||
| Function / homology | Function and homology informationviral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / Influenza A virus (A/California/04/2009(H1N1)) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Fernandez Quintero ML / Ferguson JA / Han J / Ward AB | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2025Title: Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of V3 and V3 genes. Authors: Ting-Hui Lin / Chang-Chun David Lee / Monica L Fernández-Quintero / James A Ferguson / Julianna Han / Xueyong Zhu / Wenli Yu / Jenna J Guthmiller / Florian Krammer / Patrick C Wilson / ...Authors: Ting-Hui Lin / Chang-Chun David Lee / Monica L Fernández-Quintero / James A Ferguson / Julianna Han / Xueyong Zhu / Wenli Yu / Jenna J Guthmiller / Florian Krammer / Patrick C Wilson / Andrew B Ward / Ian A Wilson / ![]() Abstract: H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine ...H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their V and V genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_46994.map.gz | 483.8 MB | EMDB map data format | |
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| Header (meta data) | emd-46994-v30.xml emd-46994.xml | 21.4 KB 21.4 KB | Display Display | EMDB header |
| Images | emd_46994.png | 132.6 KB | ||
| Filedesc metadata | emd-46994.cif.gz | 6.9 KB | ||
| Others | emd_46994_half_map_1.map.gz emd_46994_half_map_2.map.gz | 474.5 MB 474.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-46994 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-46994 | HTTPS FTP |
-Validation report
| Summary document | emd_46994_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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| Full document | emd_46994_full_validation.pdf.gz | 1.1 MB | Display | |
| Data in XML | emd_46994_validation.xml.gz | 19 KB | Display | |
| Data in CIF | emd_46994_validation.cif.gz | 22.6 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-46994 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-46994 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9dm0MC ![]() 9druC ![]() 9ds1C ![]() 9ds2C ![]() 9dscC 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_46994.map.gz / Format: CCP4 / Size: 512 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: 0.718 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_46994_half_map_1.map | ||||||||||||
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| Projections & Slices |
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| Density Histograms |
-Half map: #1
| File | emd_46994_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : Hemagglutinin CA09 homotrimer bound to anchor fab
| Entire | Name: Hemagglutinin CA09 homotrimer bound to anchor fab |
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| Components |
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-Supramolecule #1: Hemagglutinin CA09 homotrimer bound to anchor fab
| Supramolecule | Name: Hemagglutinin CA09 homotrimer bound to anchor fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: Fab
| Supramolecule | Name: Fab / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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-Supramolecule #3: Hemagglutinin HA1/2
| Supramolecule | Name: Hemagglutinin HA1/2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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-Macromolecule #1: Fab light chain
| Macromolecule | Name: Fab light chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 11.803136 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASESVS TYLAWYQKKP GQAPRLLIYD ASHRATGIPA RFSGSGSGTD FTLTISSLES EDFGVYYCQ QRSNWPPITF GQGTRLEIK |
-Macromolecule #2: Fab heavy chain
| Macromolecule | Name: Fab heavy chain / 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: 13.490038 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: QVQLVESGGG VVQPGRSLRL SCAASGFTFR IYAMHWVRQA PGKGLEWVAV ISNEGTNKYY ADSVKGRFTI SRDNSKNTLY LQMNSLRPE DAAVYYCARD PSNPPHWGNF DSWGQGTLVT VSS |
-Macromolecule #3: Hemagglutinin
| Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Influenza A virus (A/California/04/2009(H1N1)) |
| Molecular weight | Theoretical: 35.960562 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: GDTLCIGYHA NNSTDTVDTV LEKNVTVTHS VNLLEDKHNG KLCKLRGVAP LHLGKCNIAG WILGNPECES LSTASSWSYI VETPSSDNG TCYPGDFIDY EELREQLSSV SSFERFEIFP KTSSWPNHDS NKGVTAACPH AGAKSFYKNL IWLVKKGNSY P KLSKSYIN ...String: GDTLCIGYHA NNSTDTVDTV LEKNVTVTHS VNLLEDKHNG KLCKLRGVAP LHLGKCNIAG WILGNPECES LSTASSWSYI VETPSSDNG TCYPGDFIDY EELREQLSSV SSFERFEIFP KTSSWPNHDS NKGVTAACPH AGAKSFYKNL IWLVKKGNSY P KLSKSYIN DKGKEVLVLW GIHHPSTSAD QQSLYQNADT YVFVGSSRYS KKFKPEIAIR PKVRDQEGRM NYYWTLVEPG DK ITFEATG NLVVPRYAFA MERNAGSGII ISDTPVHDCN TTCQTPKGAI NTSLPFQNIH PITIGKCPKY VKSTKLRLAT GLR NIPS UniProtKB: Hemagglutinin |
-Macromolecule #4: Hemagglutinin
| Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Influenza A virus (A/California/04/2009(H1N1)) |
| Molecular weight | Theoretical: 26.516307 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DLKSTQNAID KITNKVNSVI EKMNTQFTAV GKEFNHLEKR IENLNKKVD DGFLDIWTYN AELLVLLENE RTLDYHDSNV KNLYEKVRSQ LKNNAKEIGN GCFEFYHKCD NTCMESVKNG T YDYPKYSE ...String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DLKSTQNAID KITNKVNSVI EKMNTQFTAV GKEFNHLEKR IENLNKKVD DGFLDIWTYN AELLVLLENE RTLDYHDSNV KNLYEKVRSQ LKNNAKEIGN GCFEFYHKCD NTCMESVKNG T YDYPKYSE EAKLNREEID GSGYIPEAPR DGQAYVRKDG EWVLLSTFLG SGLNDIFEAQ KIEWHEGHHH HHH UniProtKB: Hemagglutinin |
-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: 15 / 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 |
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Sample preparation
| Concentration | 0.7 mg/mL |
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| Buffer | pH: 7.4 / Details: TBS |
| Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 25 sec. |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 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) / Number grids imaged: 1 / Number real images: 3150 / Average electron dose: 44.94 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: 1.5 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 190000 |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
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Image processing
| Startup model | Type of model: INSILICO MODEL / In silico model: Ab initio reconstruction |
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| Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v4.1.2) / Number images used: 90138 |
| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
| Initial model |
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| Output model | ![]() PDB-9dm0: |
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Keywords
Homo sapiens (human)
Influenza A virus (A/California/04/2009(H1N1))
Authors
United States, 1 items
Citation











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FIELD EMISSION GUN
