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- EMDB-42530: CryoEM structure of A/Michigan/45/2015 H1 in complex with flu HA ... -
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Open data
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Basic information
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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 | |||||||||
![]() | Mich15H1 UCA6_N55T_sharp | |||||||||
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![]() | Flu Hemagglutinin / Central stem epitope / VH1-18 / 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 / 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: 3.5 Å | |||||||||
![]() | Huang J / Han J / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 203.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.9 KB 19.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.8 KB | Display | ![]() |
Images | ![]() | 52.8 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
Others | ![]() ![]() | 200.7 MB 200.7 MB | ||
Archive directory | ![]() ![]() | 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 ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Annotation | Mich15H1 UCA6_N55T_sharp | ||||||||||||||||||||
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 |
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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: ![]() |
-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: ![]() ![]() |
Molecular weight | Theoretical: 36.018465 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() ![]() |
Molecular weight | Theoretical: 28.359492 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() |
Molecular weight | Theoretical: 13.893534 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() |
Molecular weight | Theoretical: 11.858149 KDa |
Recombinant expression | Organism: ![]() |
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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![]() | single particle reconstruction |
Aggregation state | particle |
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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 |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |