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- EMDB-22937: Localized reconstruction of the H1 A/Michigan/45/2015 ectodomain ... -

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Basic information

Entry
Database: EMDB / ID: EMD-22937
TitleLocalized reconstruction of the H1 A/Michigan/45/2015 ectodomain displayed at the surface of I53_dn5 nanoparticle
Map data
Sample
  • Complex: H1 A/Michigan/45/2015 ectodomain fused to I53_dn5
    • Protein or peptide: Hemagglutinin,I53_dn5
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


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
Haemagglutinin, influenzavirus A / Haemagglutinin, HA1 chain, alpha/beta domain superfamily / Haemagglutinin / Haemagglutinin, influenzavirus A/B / Viral capsid/haemagglutinin protein
Similarity search - Domain/homology
Biological speciesInfluenza A virus / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsActon OJ / Park YJ / Veesler D / Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM120553 United States
CitationJournal: Nature / Year: 2021
Title: Quadrivalent influenza nanoparticle vaccines induce broad protection.
Authors: Seyhan Boyoglu-Barnum / Daniel Ellis / Rebecca A Gillespie / Geoffrey B Hutchinson / Young-Jun Park / Syed M Moin / Oliver J Acton / Rashmi Ravichandran / Mike Murphy / Deleah Pettie / Nick ...Authors: Seyhan Boyoglu-Barnum / Daniel Ellis / Rebecca A Gillespie / Geoffrey B Hutchinson / Young-Jun Park / Syed M Moin / Oliver J Acton / Rashmi Ravichandran / Mike Murphy / Deleah Pettie / Nick Matheson / Lauren Carter / Adrian Creanga / Michael J Watson / Sally Kephart / Sila Ataca / John R Vaile / George Ueda / Michelle C Crank / Lance Stewart / Kelly K Lee / Miklos Guttman / David Baker / John R Mascola / David Veesler / Barney S Graham / Neil P King / Masaru Kanekiyo /
Abstract: Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation ...Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines.
History
DepositionNov 4, 2020-
Header (metadata) releaseMar 31, 2021-
Map releaseMar 31, 2021-
UpdateMay 5, 2021-
Current statusMay 5, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.056
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.056
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7kna
  • Surface level: 0.056
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22937.png

Downloads & links

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Map

FileDownload / File: emd_22937.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.05 Å
Density
Contour LevelBy AUTHOR: 0.056 / Movie #1: 0.056
Minimum - Maximum-0.107380584 - 0.25371072
Average (Standard dev.)0.0004766235 (±0.005885445)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 268.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.051.051.05
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z268.800268.800268.800
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ400400400
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-0.1070.2540.000

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Supplemental data

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Additional map: #1

Fileemd_22937_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_22937_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_22937_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : H1 A/Michigan/45/2015 ectodomain fused to I53_dn5

EntireName: H1 A/Michigan/45/2015 ectodomain fused to I53_dn5
Components
  • Complex: H1 A/Michigan/45/2015 ectodomain fused to I53_dn5
    • Protein or peptide: Hemagglutinin,I53_dn5
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: H1 A/Michigan/45/2015 ectodomain fused to I53_dn5

SupramoleculeName: H1 A/Michigan/45/2015 ectodomain fused to I53_dn5 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Influenza A virus / Strain: A/Michigan/45/2015(H1N1)

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Macromolecule #1: Hemagglutinin,I53_dn5

MacromoleculeName: Hemagglutinin,I53_dn5 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 72.352695 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DTLCIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDKHNGK LCKLRGVAPL HLGKCNIAGW ILGNPECESL STASSWSYIV ETSNSDNGT CFPGDFINYE ELREQLSSVS SFERFEIFPK TSSWPNHDSN KGVTAACPHA GAKSFYKNLI WLVKKGNSYP K LNQSYIND ...String:
DTLCIGYHAN NSTDTVDTVL EKNVTVTHSV NLLEDKHNGK LCKLRGVAPL HLGKCNIAGW ILGNPECESL STASSWSYIV ETSNSDNGT CFPGDFINYE 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 RGLFGAIAGF IEGGWTGMVD GWYGYHHQNE QGSGYAADLK STQNAIDKIT NKVNSVIEKM NTQFTAVGKE FNHL EKRIE NLNKKVDDGF LDIWTYNAEL LVLLENERTL DYHDSNVKNL YEKVRNQLKN NAKEIGNGCF EFYHKCDNTC MESVK NGTY DYPKYSEEAK LNREKIDGVS AEEAELAYLL GELAYKLGEY RIAIRAYRIA LKRDPNNAEA WYNLGNAYYK QGRYRE AIE YYQKALELDP NNAEAWYNLG NAYYERGEYE EAIEYYRKAL RLDPNNADAM QNLLNAKMRE EGGWELQHHH HHH

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Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 12 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 70.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER / Details: cryoSPARC ab initio
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 148916

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