[English] 日本語

- EMDB-44112: Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal an... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008 | |||||||||
![]() | Hemagglutinin H1 NC99 in complex with the monoclonal antibody Fab43_S0008 | |||||||||
![]() |
| |||||||||
![]() | influenza virus / broadly neutralizing antibody / bnAb / VH1-69 / DH3-9 / hemagglutinin / HA / stem / stalk / germline-targeting / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() viral 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 | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
![]() | Torrents de la Pena A / de Paiva Froes Rocha R / Ward AB / Ataca S / Kanekiyo M | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem. Authors: Sila Ataca / Maya Sangesland / Rebeca de Paiva Fróes Rocha / Alba Torrents de la Peña / Larance Ronsard / Seyhan Boyoglu-Barnum / Rebecca A Gillespie / Yaroslav Tsybovsky / Tyler Stephens ...Authors: Sila Ataca / Maya Sangesland / Rebeca de Paiva Fróes Rocha / Alba Torrents de la Peña / Larance Ronsard / Seyhan Boyoglu-Barnum / Rebecca A Gillespie / Yaroslav Tsybovsky / Tyler Stephens / Syed M Moin / Julia Lederhofer / Adrian Creanga / Sarah F Andrews / Ralston M Barnes / Daniel Rohrer / Nils Lonberg / Barney S Graham / Andrew B Ward / Daniel Lingwood / Masaru Kanekiyo / ![]() Abstract: Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant ...Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response. Immunization with a non-cognate group 2 HA stem enriched B cells harboring the IGHD3-9 gene, thereby switching from IGHV1-69- to IGHD3-9-encoded motif-dependent epitope recognition. These IGHD3-9 antibodies bound, neutralized, and conferred cross-group protection in mice against influenza A viruses. A cryoelectron microscopy (cryo-EM) structure of an IGHD3-9 antibody resembled the human broadly neutralizing antibody FI6v3, which uses IGHD3-9. Together, our findings offer insights into vaccine regimens that engage an immunoglobulin repertoire with broader cross-reactivity to influenza A viruses. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 118.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 23.7 KB 23.7 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.5 KB | Display | ![]() |
Images | ![]() | 50.5 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() ![]() | 62.4 MB 115.9 MB 115.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9b2mMC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Hemagglutinin H1 NC99 in complex with the monoclonal antibody Fab43_S0008 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: Hemagglutinin H1 NC99 in complex with the monoclonal...
File | emd_44112_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Hemagglutinin H1 NC99 in complex with the monoclonal antibody Fab43_S0008 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Hemagglutinin H1 NC99 in complex with the monoclonal...
File | emd_44112_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Hemagglutinin H1 NC99 in complex with the monoclonal antibody Fab43_S0008 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Hemagglutinin H1 NC99 in complex with the monoclonal...
File | emd_44112_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Hemagglutinin H1 NC99 in complex with the monoclonal antibody Fab43_S0008 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal an...
Entire | Name: Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008 |
---|---|
Components |
|
-Supramolecule #1: Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal an...
Supramolecule | Name: Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #2-#4 Details: Fab fragment was generated using papain digestion and size exclusion chromatography. The complex was incubated overnight and the sample was purified using size exclusion chromatography |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 330 KDa |
-Macromolecule #1: Hemagglutinin HA1 chain
Macromolecule | Name: Hemagglutinin HA1 chain / type: protein_or_peptide / ID: 1 / Details: Hemagglutinin New Caledonia 1999 HA1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 37.803648 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKAKLLVLLC TFTATYADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCL LKGIAPLQLG NCSVAGWILG NPECELLIS KESWSYIVET PNPENGTCYP GYFADYEELR EQLSSVSSFE RFEIFPKESS WPNHTVTGVS ASCSHNGKSS F YRNLLWLT ...String: MKAKLLVLLC TFTATYADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCL LKGIAPLQLG NCSVAGWILG NPECELLIS KESWSYIVET PNPENGTCYP GYFADYEELR EQLSSVSSFE RFEIFPKESS WPNHTVTGVS ASCSHNGKSS F YRNLLWLT GKNGLYPNLS KSYVNNKEKE VLVLWGVHHP PNIGNQRALY HTENAYVSVV SSHYSRRFTP EIAKRPKVRD QE GRINYYW TLLEPGDTII FEANGNLIAP WYAFALSRGF GSGIITSNAP MDECDAKCQT PQGAINSSLP FQNVHPVTIG ECP KYVRSA KLRMVTGLRN IPS UniProtKB: Hemagglutinin |
-Macromolecule #2: Hemagglutinin HA2 chain
Macromolecule | Name: Hemagglutinin HA2 chain / type: protein_or_peptide / ID: 2 / Details: Hemagglutinin H1 New Caledonia 1999 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.550836 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DQKSTQNAIN GITNKVNSVI EKMNTQFTAV GKEFNKLERR MENLNKKVD DGFLDIWTYN AELLVLLENE RTLDFHDSNV KNLYEKVKSQ LKNNAKEIGN GCFEFYHKCN NECMESVKNG T YDYPKYSE ...String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DQKSTQNAIN GITNKVNSVI EKMNTQFTAV GKEFNKLERR MENLNKKVD DGFLDIWTYN AELLVLLENE RTLDFHDSNV KNLYEKVKSQ LKNNAKEIGN GCFEFYHKCN NECMESVKNG T YDYPKYSE ESKLNREKID GVKLESMGVY QILAIYSTVA SSLVLLVSLG AISFWMCSNG SLQCRICI UniProtKB: Hemagglutinin |
-Macromolecule #3: Heavy chain monoclonal antibody Fab 3_S0008
Macromolecule | Name: Heavy chain monoclonal antibody Fab 3_S0008 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.914199 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFR TFGISWVRQA PGQGLEWMGW IIPIIGTPNY AQKFQGRVII TADESSNTAY MELNSLKSE DTAVYYCAKE GRALLRYFDW LPLDAFDIWG QGTMVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String: QVQLVQSGAE VKKPGSSVKV SCKASGGTFR TFGISWVRQA PGQGLEWMGW IIPIIGTPNY AQKFQGRVII TADESSNTAY MELNSLKSE DTAVYYCAKE GRALLRYFDW LPLDAFDIWG QGTMVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDK |
-Macromolecule #4: Light chain monoclonal antibody Fab 3_S0008
Macromolecule | Name: Light chain monoclonal antibody Fab 3_S0008 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.034838 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIVLTQTPLS LPVSLGDQAS ISCRSSQSLV HSDGNTYLHW YLQKPGQSPK LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDLG VYFCSQSTHV PPLTFGAGTK LELKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES ...String: DIVLTQTPLS LPVSLGDQAS ISCRSSQSLV HSDGNTYLHW YLQKPGQSPK LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDLG VYFCSQSTHV PPLTFGAGTK LELKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA L QSGNSQES VTEQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNRG EC |
-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: 15 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 2 mg/mL |
---|---|
Buffer | pH: 7.4 / Details: TBS |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 7 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 40 K / Instrument: FEI VITROBOT MARK IV |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 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 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |