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- EMDB-21973: CryoEM structure of influenza hemagglutinin A/Victoria/361/2011 i... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21973 | |||||||||
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Title | CryoEM structure of influenza hemagglutinin A/Victoria/361/2011 in complex with cyno antibody 3B10 | |||||||||
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Function / homology | ![]() viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / membrane => GO:0016020 / 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 | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.7 Å | |||||||||
![]() | Qiu Y / Zhou Y / Darricarrere N | |||||||||
![]() | ![]() Title: Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates. Authors: Nicole Darricarrère / Yu Qiu / Masaru Kanekiyo / Adrian Creanga / Rebecca A Gillespie / Syed M Moin / Jacqueline Saleh / Jose Sancho / Te-Hui Chou / Yanfeng Zhou / Ruijun Zhang / Shujia Dai ...Authors: Nicole Darricarrère / Yu Qiu / Masaru Kanekiyo / Adrian Creanga / Rebecca A Gillespie / Syed M Moin / Jacqueline Saleh / Jose Sancho / Te-Hui Chou / Yanfeng Zhou / Ruijun Zhang / Shujia Dai / Anthony Moody / Kevin O Saunders / Michelle C Crank / John R Mascola / Barney S Graham / Chih-Jen Wei / Gary J Nabel / ![]() Abstract: Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most ...Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus-associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 5.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.3 KB 14.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9 KB | Display | ![]() |
Images | ![]() | 67 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wztMC ![]() 6xgcC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Influenza hemagglutinin A/Victoria/361/2011 in complex with 3B10 Fab
Entire | Name: Influenza hemagglutinin A/Victoria/361/2011 in complex with 3B10 Fab |
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Components |
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-Supramolecule #1: Influenza hemagglutinin A/Victoria/361/2011 in complex with 3B10 Fab
Supramolecule | Name: Influenza hemagglutinin A/Victoria/361/2011 in complex with 3B10 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 336 KDa |
-Supramolecule #2: Hemagglutinin
Supramolecule | Name: Hemagglutinin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Cyno antibody
Supramolecule | Name: Cyno antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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-Macromolecule #1: Hemagglutinin
Macromolecule | Name: Hemagglutinin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() Strain: A/reassortant/NYMC X-217(A/Puerto Rico/8/1934 x A/Victoria/361/2011)(H3N2) |
Molecular weight | Theoretical: 56.721504 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QKLPGNDNST ATLCLGHHAV PNGTIVKTIT NDQIEVTNAT ELVQNSSIGE ICDSPHQILD GENCTLIDAL LGDPQCDGFQ NKKWDLFVE RSKAYSNCFP YDVPDYASLR SLVASSGTLE FNNESFNWTG VTQNGTSSAC IRRSNNSFFS RLNWLTQLNF K YPALNVTM ...String: QKLPGNDNST ATLCLGHHAV PNGTIVKTIT NDQIEVTNAT ELVQNSSIGE ICDSPHQILD GENCTLIDAL LGDPQCDGFQ NKKWDLFVE RSKAYSNCFP YDVPDYASLR SLVASSGTLE FNNESFNWTG VTQNGTSSAC IRRSNNSFFS RLNWLTQLNF K YPALNVTM PNNEQFDKLY IWGVHHPVTD KDQIFLYAQS SGRITVSTKR SQQAVIPNIG YRPRIRNIPS RISIYWTIVK PG DILLINS TGNLIAPRGY FKIRSGKSSI MRSDAPIGKC NSECITPNGS IPNDKPFQNV NRITYGACPR YVKQSTLKLA TGM RNVPEK QTRGIFGAIA GFIENGWEGM VDGWYGFRHQ NSEGRGQAAD LKSTQAAIDQ INGKLNRLIG KTNEKFHQIE KEFS EVEGR IQDLEKYVED TKIDLWSYNA ELLVALENQH TIDLTDSEMN KLFEKTKKQL RENAEDMGNG CFKIYHKCDN ACIGS IRNG TYDHDVYRDE ALNNRFQIK |
-Macromolecule #2: Cyno antibody heavy chain
Macromolecule | Name: Cyno antibody heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.700625 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLQESGPG LVKPSETLSL TCAVSGGTFS AYYWGWIRQP PGKGLEWIGS ISGGSGSTDY SPSLKSRATI SRDTSKNQFS LKLTSVTAA DTAVYYCVRK YWGDYYANWF DVWGPGVLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV T VSWNSGSL ...String: QVQLQESGPG LVKPSETLSL TCAVSGGTFS AYYWGWIRQP PGKGLEWIGS ISGGSGSTDY SPSLKSRATI SRDTSKNQFS LKLTSVTAA DTAVYYCVRK YWGDYYANWF DVWGPGVLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV T VSWNSGSL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYVCNVN HKPSNTKVDK RVEIKTCGGG SKPPT |
-Macromolecule #3: Cyno antibody light chain
Macromolecule | Name: Cyno antibody light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.095521 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQMTQSPSS LSASVGDTVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASSLQGGVPS RFSGSGSGSD FTLTISSLQS EDFATYYCQ QYSGRPPTFG QGTKVEIKRA VAAPSVFIFP PSEDQVKSGT VSVVCLLNNF YPREASVKWK VDGALKTGNS Q ESVTEQDS ...String: DIQMTQSPSS LSASVGDTVT ITCRASQSIS SWLAWYQQKP GKAPKLLIYK ASSLQGGVPS RFSGSGSGSD FTLTISSLQS EDFATYYCQ QYSGRPPTFG QGTKVEIKRA VAAPSVFIFP PSEDQVKSGT VSVVCLLNNF YPREASVKWK VDGALKTGNS Q ESVTEQDS KDNTYSLSST LTLSSTDYQS HNVYACEVTH QGLSSPVTKS FNRGEC |
-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: 3 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.13 mg/mL |
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Buffer | pH: 8.5 |
Grid | Model: C-flat-2/2 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |