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- EMDB-22180: CryoEM structure of influenza hemagglutinin A/Michigan/45/2015 in... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22180 | |||||||||
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Title | CryoEM structure of influenza hemagglutinin A/Michigan/45/2015 in complex with cyno antibody 1C4 | |||||||||
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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: 4.1 Å | |||||||||
![]() | Qiu Y / Zhou Y | |||||||||
![]() | ![]() 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 | ![]() | 8.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.1 KB 15.1 KB | Display Display | ![]() |
Images | ![]() | 77.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6xgcMC ![]() 6wztC 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: 1.059 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 : A/Michigan/45/2015(H1N1) hemagglutinin in complex with 1C4 Fab
Entire | Name: A/Michigan/45/2015(H1N1) hemagglutinin in complex with 1C4 Fab |
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Components |
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-Supramolecule #1: A/Michigan/45/2015(H1N1) hemagglutinin in complex with 1C4 Fab
Supramolecule | Name: A/Michigan/45/2015(H1N1) hemagglutinin in complex with 1C4 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Molecular weight | Theoretical: 320 kDa/nm |
-Supramolecule #2: Hemagglutinin
Supramolecule | Name: Hemagglutinin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: 1C4 Fab
Supramolecule | Name: 1C4 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 36.432949 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DTLCIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDKHNGK LCKLRGVAPL HLGKCNIAGW ILGNPECESL STASSWSYIV ETSNSDNGT CYPGDFINYE ELREQLSSVS SFERFEIFPK TSSWPNHDSN KGVTAACPHA GAKSFYKNLI WLVKKGNSYP K LNQSYIND ...String: DTLCIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDKHNGK LCKLRGVAPL HLGKCNIAGW ILGNPECESL STASSWSYIV ETSNSDNGT CYPGDFINYE ELREQLSSVS SFERFEIFPK TSSWPNHDSN KGVTAACPHA GAKSFYKNLI WLVKKGNSYP K LNQSYIND KGKEVLVLWG IHHPSTTADQ QSLYQNADAY VFVGTSRYSK KFKPEIATRP KVRDQEGRMN YYWTLVEPGD KI TFEATGN LVVPRYAFTM ERNAGSGIII SDTPVHDCNT TCQTPEGAIN TSLPFQNIHP ITIGKCPKYV KSTKLRLATG LRN VPSIQS 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: ![]() |
Molecular weight | Theoretical: 25.109902 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GLFGAIAGFI EGGWTGMVDG WYGYHHQNEQ GSGYAADLKS TQNAIDKITN KVNSVIEKMN TQFTAVGKEF NHLEKRIENL NKKVDDGFL DIWTYNAELL VLLENERTLD YHDSNVKNLY EKVRNQLKNN AKEIGNGCFE FYHKCDNTCM ESVKNGTYDY P KYSEEAKL ...String: GLFGAIAGFI EGGWTGMVDG WYGYHHQNEQ GSGYAADLKS TQNAIDKITN KVNSVIEKMN TQFTAVGKEF NHLEKRIENL NKKVDDGFL DIWTYNAELL VLLENERTLD YHDSNVKNLY EKVRNQLKNN AKEIGNGCFE FYHKCDNTCM ESVKNGTYDY P KYSEEAKL NREKIDSGRL VPRGSPGSGY IPEAPRDGQA YVRKDGEWVL LSTFLGHHHH HH |
-Macromolecule #3: 1C4 Fab heavy chain
Macromolecule | Name: 1C4 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 25.605572 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLVESGGG LAKPGGSLRL SCAASGFTFS TYAMHWVRQA PGKGLEWISG INSGGGSTWY TASVKGRFTI SRDNSKSTLS LQMNSLRTE DTAVYYCAKD GGNAIFGLVI TNYGLDSWGQ GAVVTVSSAS TKGPSVFPLA PSSRSTSEST AALGCLVKDY F PEPVTVSW ...String: EVQLVESGGG LAKPGGSLRL SCAASGFTFS TYAMHWVRQA PGKGLEWISG INSGGGSTWY TASVKGRFTI SRDNSKSTLS LQMNSLRTE DTAVYYCAKD GGNAIFGLVI TNYGLDSWGQ GAVVTVSSAS TKGPSVFPLA PSSRSTSEST AALGCLVKDY F PEPVTVSW NSGSLTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY VCNVNHKPSN TKVDKRVEIK TCGGGSKPPT HH HHHH |
-Macromolecule #4: 1C4 Fab light chain
Macromolecule | Name: 1C4 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.837086 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QSVLTQPPSA SGAPGQSVTI SCSGSSSNFG SNHVYWYQQL SGKAPKLLIY NNNRRPSGVP DRFSGSKSGT SASLAISGLQ SEDEADYYC SVWDSSLNNV LFGGGTRLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGVVK VAWKADGNSV N TGVETTTP ...String: QSVLTQPPSA SGAPGQSVTI SCSGSSSNFG SNHVYWYQQL SGKAPKLLIY NNNRRPSGVP DRFSGSKSGT SASLAISGLQ SEDEADYYC SVWDSSLNNV LFGGGTRLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGVVK VAWKADGNSV N TGVETTTP SKQSNNKYAA SSYLSLTSDQ WKSHKSYSCQ VTHEGSTVEK TVAPAECS |
-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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 449762 |
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Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |