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Yorodumi- EMDB-21961: Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited,... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21961 | |||||||||
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Title | Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 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 Similarity search - Function | |||||||||
Biological species | Influenza A virus / Homo sapiens (human) / Influenza A virus (A/Shanghai/JS01/2013(H7N9)) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.76 Å | |||||||||
Authors | Gorman J / Kwong PD | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Structure / Year: 2022 Title: Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite. Authors: Crystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting ...Authors: Crystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting Teng / Raffaello Verardi / Shuishu Wang / Yongping Yang / Gwo-Yu Chuang / Adrian B McDermott / Tongqing Zhou / Peter D Kwong / Abstract: Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, ...Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite. | |||||||||
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_21961.map.gz | 228 MB | EMDB map data format | |
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Header (meta data) | emd-21961-v30.xml emd-21961.xml | 24.9 KB 24.9 KB | Display Display | EMDB header |
Images | emd_21961.png | 59.7 KB | ||
Masks | emd_21961_msk_1.map | 244.1 MB | Mask map | |
Others | emd_21961_additional_1.map.gz emd_21961_half_map_1.map.gz emd_21961_half_map_2.map.gz | 52.5 MB 226.3 MB 226.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21961 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21961 | HTTPS FTP |
-Related structure data
Related structure data | 6wxlMC 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_21961.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.083 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_21961_msk_1.map | ||||||||||||
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-Additional map: Unsharpened map
File | emd_21961_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
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-Half map: Halfmap A
File | emd_21961_half_map_1.map | ||||||||||||
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Annotation | Halfmap A | ||||||||||||
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-Half map: Halfmap B
File | emd_21961_half_map_2.map | ||||||||||||
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Annotation | Halfmap B | ||||||||||||
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Density Histograms |
-Sample components
-Entire : 1D12 in complex with an H7 SH13 HA trimer
Entire | Name: 1D12 in complex with an H7 SH13 HA trimer |
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Components |
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-Supramolecule #1: 1D12 in complex with an H7 SH13 HA trimer
Supramolecule | Name: 1D12 in complex with an H7 SH13 HA trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: H7 SH13 HA trimer
Supramolecule | Name: H7 SH13 HA trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Influenza A virus |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: 1D12 Fab
Supramolecule | Name: 1D12 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
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 (A/Shanghai/JS01/2013(H7N9)) / Strain: A/Shanghai/JS01/2013(H7N9) |
Molecular weight | Theoretical: 35.039473 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DKICLGHHAV SNGTKVNTLT ERGVEVVNAT ETVERTNIPR ICSKGKRTVD LGQCGLLGTI TGPPQCDQFL EFSADLIIER REGSDVCYP GKFVNEEALR QILRESGGID KEAMGFTYSG IRTNGATSSC RRSGSSFYAE MKWLLSNTDN AAFPQMTKSY K NTRKNPAL ...String: DKICLGHHAV SNGTKVNTLT ERGVEVVNAT ETVERTNIPR ICSKGKRTVD LGQCGLLGTI TGPPQCDQFL EFSADLIIER REGSDVCYP GKFVNEEALR QILRESGGID KEAMGFTYSG IRTNGATSSC RRSGSSFYAE MKWLLSNTDN AAFPQMTKSY K NTRKNPAL IVWGIHHSGS TAEQTKLYGS GNKLVTVGSS NYQQSFVPSP GARTQVNGQS GRIDFHWLML NPNDTVTFSF NG AFIAPDR ASFLRGKSMG IQSGVQVDAD CEGDCYYSGG TIISNLPFQN IDSRAVGKCP RYVKQRSLLL ATGMKNVPEI PKG R |
-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 (A/Shanghai/JS01/2013(H7N9)) / Strain: A/Shanghai/JS01/2013(H7N9) |
Molecular weight | Theoretical: 25.234352 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GLFGAIAGFI ENGWEGLIDG WYGFRHQNAQ GEGTAADYKS TQSAIDQITG KLNRLIEKTN QQFELIDNEF TEVEKQIGNV INWTRDSIT EVWSYNAELL VAMENQHTID LADSEMDKLY ERVKRQLREN AEEDGTGCFE IFHKCDDDCM ASIRNNTYDH S KYREEAMQ ...String: GLFGAIAGFI ENGWEGLIDG WYGFRHQNAQ GEGTAADYKS TQSAIDQITG KLNRLIEKTN QQFELIDNEF TEVEKQIGNV INWTRDSIT EVWSYNAELL VAMENQHTID LADSEMDKLY ERVKRQLREN AEEDGTGCFE IFHKCDDDCM ASIRNNTYDH S KYREEAMQ NRIQIDPVKL SSGYKDVILW FSFGASCFIL LAIAMGLVFI CVKNGNMRCT ICI |
-Macromolecule #3: 1D12 Light chain
Macromolecule | Name: 1D12 Light chain / 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: 23.971762 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSPLS LSVTPGEPAS ISCRSSHSLL HLNGYNYLDW YLQKPGQSPQ LLIYLGSNRA SGVPDRFSGS GSGTDFTLKI SRVEAEDVG IYYCMQALRT PPGLTFGGGT KVDIKRTVAA PSVFIFPPSE DQVKSGTVSV VCLLNNFYPR EASVKWKVDG A LKTGNSQE ...String: DIVMTQSPLS LSVTPGEPAS ISCRSSHSLL HLNGYNYLDW YLQKPGQSPQ LLIYLGSNRA SGVPDRFSGS GSGTDFTLKI SRVEAEDVG IYYCMQALRT PPGLTFGGGT KVDIKRTVAA PSVFIFPPSE DQVKSGTVSV VCLLNNFYPR EASVKWKVDG A LKTGNSQE SVTEQDSKDN TYSLSSTLTL SSTEYQSHKV YACEVTHQGL SSPVTKSFNR GEC |
-Macromolecule #4: 1D21 Heavy chain
Macromolecule | Name: 1D21 Heavy chain / 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: 25.042229 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QLVQSGAEVK KPGASVKVSC KASGYTFTGY YLHWVRQAPG QGLEWMGRIN PDTGGTNYAQ KFQGRVSMTR DMSISTHYME LSRLTSDDT AVYYCATKRG AVTAMVYYYF YGMDVWGQGT TVTVSSASTK GPSVFPLAPS SESTAALGCL VKDYFPEPVT V SWNSGSLT ...String: QLVQSGAEVK KPGASVKVSC KASGYTFTGY YLHWVRQAPG QGLEWMGRIN PDTGGTNYAQ KFQGRVSMTR DMSISTHYME LSRLTSDDT AVYYCATKRG AVTAMVYYYF YGMDVWGQGT TVTVSSASTK GPSVFPLAPS SESTAALGCL VKDYFPEPVT V SWNSGSLT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYVCNVNH KPSNTKVDKR VEIKTCGGLE VLFQ |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 9 / 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 |
Grid | Model: C-flat-1.2/1.3 4C / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
Details | Cryo-EM structure of the VRC315 clinical trial, vaccine-elicited, human antibody 1D12 in complex with an H7 SH13 HA trimer |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 1878 / Average exposure time: 2.0 sec. / Average electron dose: 49.9 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |