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Yorodumi- EMDB-42530: CryoEM structure of A/Michigan/45/2015 H1 in complex with flu HA ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-42530 | |||||||||
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Title | CryoEM structure of A/Michigan/45/2015 H1 in complex with flu HA central stem VH1-18 antibody UCA6_N55T | |||||||||
Map data | Mich15H1 UCA6_N55T_sharp | |||||||||
Sample |
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Keywords | Flu Hemagglutinin / Central stem epitope / VH1-18 / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
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 | Homo sapiens (human) / Influenza A virus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Huang J / Han J / Ward AB | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Immunity / Year: 2024 Title: Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses. Authors: Rashmi Ray / Faez Amokrane Nait Mohamed / Daniel P Maurer / Jiachen Huang / Berk A Alpay / Larance Ronsard / Zhenfei Xie / Julianna Han / Monica Fernandez-Quintero / Quynh Anh Phan / Rebecca ...Authors: Rashmi Ray / Faez Amokrane Nait Mohamed / Daniel P Maurer / Jiachen Huang / Berk A Alpay / Larance Ronsard / Zhenfei Xie / Julianna Han / Monica Fernandez-Quintero / Quynh Anh Phan / Rebecca L Ursin / Mya Vu / Kathrin H Kirsch / Thavaleak Prum / Victoria C Rosado / Thalia Bracamonte-Moreno / Vintus Okonkwo / Julia Bals / Caitlin McCarthy / Usha Nair / Masaru Kanekiyo / Andrew B Ward / Aaron G Schmidt / Facundo D Batista / Daniel Lingwood / Abstract: Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, ...Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_42530.map.gz | 203.8 MB | EMDB map data format | |
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Header (meta data) | emd-42530-v30.xml emd-42530.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_42530_fsc.xml | 12.8 KB | Display | FSC data file |
Images | emd_42530.png | 52.8 KB | ||
Filedesc metadata | emd-42530.cif.gz | 6.3 KB | ||
Others | emd_42530_half_map_1.map.gz emd_42530_half_map_2.map.gz | 200.7 MB 200.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42530 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42530 | HTTPS FTP |
-Validation report
Summary document | emd_42530_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_42530_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_42530_validation.xml.gz | 21.5 KB | Display | |
Data in CIF | emd_42530_validation.cif.gz | 27.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42530 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42530 | HTTPS FTP |
-Related structure data
Related structure data | 8ut5MC 8ut3C 8ut4C 8ut6C 8ut7C 8ut8C 8ut9C 8uwaC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_42530.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Mich15H1 UCA6_N55T_sharp | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.725 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Mich15H1 UCA6 N55T halfA
File | emd_42530_half_map_1.map | ||||||||||||
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Annotation | Mich15H1 UCA6_N55T_halfA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Mich15H1 UCA6 N55T halfA
File | emd_42530_half_map_2.map | ||||||||||||
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Annotation | Mich15H1 UCA6_N55T_halfA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : An UCA6 Fab complex with one protomer of a H3 trimer
Entire | Name: An UCA6 Fab complex with one protomer of a H3 trimer |
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Components |
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-Supramolecule #1: An UCA6 Fab complex with one protomer of a H3 trimer
Supramolecule | Name: An UCA6 Fab complex with one protomer of a H3 trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Hemagglutinin HA1 chain
Macromolecule | Name: Hemagglutinin HA1 chain / type: protein_or_peptide / ID: 1 / Details: A/Michigan/45/2015 H1 HA1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus |
Molecular weight | Theoretical: 36.018465 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: ADTLCIGYHA NNSTDTVDTV LEKNVTVTHS VNLLEDKHNG KLCKLRGVAP LHLGKCNIAG WILGNPECES LSTASSWSYI VETSNSDNG TCYPGDFINY EELREQLSSV SSFERFEIFP KTSSWPNHDS NKGVTAACPH AGAKSFYKNL IWLVKKGNSY P KLNQSYIN ...String: ADTLCIGYHA NNSTDTVDTV LEKNVTVTHS VNLLEDKHNG KLCKLRGVAP LHLGKCNIAG WILGNPECES LSTASSWSYI VETSNSDNG TCYPGDFINY EELREQLSSV SSFERFEIFP KTSSWPNHDS NKGVTAACPH AGAKSFYKNL IWLVKKGNSY P KLNQSYIN DKGKEVLVLW GIHHPSTTAD QQSLYQNADA YVFVGTSRYS KKFKPEIATR PKVRDQEGRM NYYWTLVEPG DK ITFEATG NLVVPRYAFT MERNAGSGII ISDTPVHDCN TTCQTPEGAI NTSLPFQNIH PITIGKCPKY VKSTKLRLAT GLR NVPS UniProtKB: Hemagglutinin |
-Macromolecule #2: Hemagglutinin HA2 chain
Macromolecule | Name: Hemagglutinin HA2 chain / type: protein_or_peptide / ID: 2 / Details: A/Michigan/45/2015 H1 HA2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Influenza A virus |
Molecular weight | Theoretical: 28.359492 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DLKSTQNAID KITNKVNSVI EKMNTQFTAV GKEFNHLEKR IENLNKKVD DGFLDIWTYN AELLVLLENE RTLDYHDSNV KNLYEKVRNQ LKNNAKEIGN GCFEFYHKCD NTCMESVKNG T YDYPKYSE ...String: IQSRGLFGAI AGFIEGGWTG MVDGWYGYHH QNEQGSGYAA DLKSTQNAID KITNKVNSVI EKMNTQFTAV GKEFNHLEKR IENLNKKVD DGFLDIWTYN AELLVLLENE RTLDYHDSNV KNLYEKVRNQ LKNNAKEIGN GCFEFYHKCD NTCMESVKNG T YDYPKYSE EAKLNREKID GVKGALEVLF QGPGSHHHHH HHHLGGSGYI PEAPRDGQAY VRKDGEWVLL STFLGSGGGL ND IFEAQKI EWH UniProtKB: Hemagglutinin |
-Macromolecule #3: UCA6_N55T HC Fv
Macromolecule | Name: UCA6_N55T HC Fv / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.893534 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYGISWVRQA PGQGLEWMGW ISAYTGNTNY AQKLQGRVTM TTDTSTSTAY MELRSLRSD DTAVYYCARG LLQGVVILDS YYYTMDVWGQ GTTVTVSS |
-Macromolecule #4: UCA6_N55T LC Fv
Macromolecule | Name: UCA6_N55T LC Fv / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.858149 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVS SSYLAWYQQK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYGSSPRWT FGQGTKLEIK |
-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: 17 / 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 | 0.7 mg/mL | ||||||||
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Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |