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Yorodumi- EMDB-23816: Cryo-EM structure of the VRC310 clinical trial, vaccine-elicited,... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23816 | |||||||||
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Title | Cryo-EM structure of the VRC310 clinical trial, vaccine-elicited, human antibody 310-030-1D06 Fab in complex with an H1 NC99 HA trimer | |||||||||
Map data | sharpened map | |||||||||
Sample |
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Function / homology | Function and homology information viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / apical plasma membrane / 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 | Influenza A virus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.87 Å | |||||||||
Authors | Gorman J / Kwong PD | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Med / Year: 2022 Title: A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. Authors: Sarah F Andrews / Julie E Raab / Jason Gorman / Rebecca A Gillespie / Crystal S F Cheung / Reda Rawi / Lauren Y Cominsky / Jeffrey C Boyington / Adrian Creanga / Chen-Hsiang Shen / Darcy R ...Authors: Sarah F Andrews / Julie E Raab / Jason Gorman / Rebecca A Gillespie / Crystal S F Cheung / Reda Rawi / Lauren Y Cominsky / Jeffrey C Boyington / Adrian Creanga / Chen-Hsiang Shen / Darcy R Harris / Adam S Olia / Alexandra F Nazzari / Tongqing Zhou / Katherine V Houser / Grace L Chen / John R Mascola / Barney S Graham / Masaru Kanekiyo / Julie E Ledgerwood / Peter D Kwong / Adrian B McDermott / Abstract: Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem- ...Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23816.map.gz | 108.6 MB | EMDB map data format | |
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Header (meta data) | emd-23816-v30.xml emd-23816.xml | 23.3 KB 23.3 KB | Display Display | EMDB header |
Images | emd_23816.png | 107.8 KB | ||
Masks | emd_23816_msk_1.map | 115.9 MB | Mask map | |
Others | emd_23816_additional_1.map.gz emd_23816_additional_2.map.gz emd_23816_half_map_1.map.gz emd_23816_half_map_2.map.gz | 24.5 MB 22.5 MB 107.7 MB 107.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23816 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23816 | HTTPS FTP |
-Validation report
Summary document | emd_23816_validation.pdf.gz | 826 KB | Display | EMDB validaton report |
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Full document | emd_23816_full_validation.pdf.gz | 825.5 KB | Display | |
Data in XML | emd_23816_validation.xml.gz | 13.5 KB | Display | |
Data in CIF | emd_23816_validation.cif.gz | 15.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23816 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23816 | HTTPS FTP |
-Related structure data
Related structure data | 7mfgMC 7l0lC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23816.map.gz / Format: CCP4 / Size: 115.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07325 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_23816_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map
File | emd_23816_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: density modified with resolve
File | emd_23816_additional_2.map | ||||||||||||
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Annotation | density modified with resolve | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_23816_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_23816_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 310-030-1D06 Fab in complex with an H1 NC99 HA trimer
Entire | Name: 310-030-1D06 Fab in complex with an H1 NC99 HA trimer |
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Components |
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-Supramolecule #1: 310-030-1D06 Fab in complex with an H1 NC99 HA trimer
Supramolecule | Name: 310-030-1D06 Fab in complex with an H1 NC99 HA trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Influenza A virus |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Hemagglutinin HA1 chain
Macromolecule | Name: Hemagglutinin HA1 chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus |
Molecular weight | Theoretical: 36.407852 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DTICIGYHAN NSTDTVDTVC EKNVTVTHSV NLLEDSHNGK LCLLKGIAPL QLGNCSVAGW ILGNPECELL ISKESWSYIV ETPNPENGT CYPGYFADYE ELREQLSSVS SFERFEIFPK ESSWPNHTVT GVSASCSHNG KSSFYRNLLW LTGKNGLYPN L SKSYVNNK ...String: DTICIGYHAN NSTDTVDTVC EKNVTVTHSV NLLEDSHNGK LCLLKGIAPL QLGNCSVAGW ILGNPECELL ISKESWSYIV ETPNPENGT CYPGYFADYE ELREQLSSVS SFERFEIFPK ESSWPNHTVT GVSASCSHNG KSSFYRNLLW LTGKNGLYPN L SKSYVNNK EKEVLVLWGV HHPPNIGNQR ALYHTENAYV SVVSSHYSRR FTPEIAKRPK VRDQEGRINY YWTLLEPGDT II FEANGNL IAPWYAFALS RGFGSGIITS NAPMDECDAK CQTPQGAINS SLPFQNVHPV TIGECPKYVR SAKLRMVTGL RNI PSIQSR |
-Macromolecule #2: Hemagglutinin HA2 chain
Macromolecule | Name: Hemagglutinin HA2 chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus |
Molecular weight | Theoretical: 25.263104 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GLFGAIAGFI EGGWTGMVDG WYGYHHQNEQ GSGYAADQKS TQNAINCITN KVNSVIEKMN TQFTAVGKEF NKLERRMENL NKKVDDGFL DIWTYNAELL VLLENERTLD FHDSNVKNLY EKVKSQLKNN AKEIGNGCFE FYHKCNNECM ESVKNGTYDY P KYSEESKL ...String: GLFGAIAGFI EGGWTGMVDG WYGYHHQNEQ GSGYAADQKS TQNAINCITN KVNSVIEKMN TQFTAVGKEF NKLERRMENL NKKVDDGFL DIWTYNAELL VLLENERTLD FHDSNVKNLY EKVKSQLKNN AKEIGNGCFE FYHKCNNECM ESVKNGTYDY P KYSEESKL NREKIDGVSG RLVPRGSPGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGHH HHHH |
-Macromolecule #3: 310-030-1D06 Heavy
Macromolecule | Name: 310-030-1D06 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: 13.000457 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFS SYGISWVRQA PGQGLEWMGG IIGMFGTTNY AQKFQGRVTI TADEFTSTAY MELSSLRSE DTAVYYCARG GSYYVDYFHH WGQGTLVTVS S |
-Macromolecule #4: 310-030-1D06 Light
Macromolecule | Name: 310-030-1D06 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: 11.658904 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLFSGERAT LSCRASQSVS SSSLAWYQQK HGQGPRLIMY GASSRATGIP DRFSGSGFGT DFTITISRLE PEDFAVYYC QQYGSSSGTF GQGTKLEMK |
-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: 21 / 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 | 2 mg/mL |
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Buffer | pH: 7.4 / Component - Formula: PBS |
Vitrification | Cryogen name: ETHANE |
Details | 310-030-1D06 Fab in complex with an H1 NC99 HA trimer |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.13 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.87 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 36235 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | PDB-7mfg: |