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- EMDB-63103: CryoEM structure of H7 hemagglutinin in complex with a human neut... -

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Basic information

Entry
Database: EMDB / ID: EMD-63103
TitleCryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13
Map data
Sample
  • Complex: CryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13
    • Complex: H7 hemagglutinin
      • Protein or peptide: Hemagglutinin
    • Complex: antibody 6Y13
      • Protein or peptide: scFv of 6Y13 chimera
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsViral protein
Function / homology
Function and homology information


viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / 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 / 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 (A/duck/Chiba/25-51-14/2013(H7N1)) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsWang M / Yuan B / Peng Q / Gao GF / Shi Y
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32192452 China
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head.
Authors: Junxin Li / Min Wang / Yang Yang / Limin Zhang / Lvyan Liu / Wei Yang / Yun Peng / Xu Zhang / Bin Yuan / Qi Peng / Xiaolu Yang / Yixin Chen / George F Gao / Yi Shi / Xiaochun Wan /
Abstract: Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing ...Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.
History
DepositionJan 13, 2025-
Header (metadata) releaseDec 3, 2025-
Map releaseDec 3, 2025-
UpdateDec 3, 2025-
Current statusDec 3, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_63103.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.04 Å/pix.
x 256 pix.
= 266.24 Å
1.04 Å/pix.
x 256 pix.
= 266.24 Å
1.04 Å/pix.
x 256 pix.
= 266.24 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.04 Å
Density
Contour LevelBy AUTHOR: 0.0103
Minimum - Maximum-0.001761298 - 1.796981
Average (Standard dev.)0.0022429584 (±0.035589233)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 266.24 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_63103_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_63103_half_map_2.map
Projections & Slices
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Sample components

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Entire : CryoEM structure of H7 hemagglutinin in complex with a human neut...

EntireName: CryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13
Components
  • Complex: CryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13
    • Complex: H7 hemagglutinin
      • Protein or peptide: Hemagglutinin
    • Complex: antibody 6Y13
      • Protein or peptide: scFv of 6Y13 chimera
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: CryoEM structure of H7 hemagglutinin in complex with a human neut...

SupramoleculeName: CryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Influenza A virus (A/duck/Chiba/25-51-14/2013(H7N1))

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Supramolecule #2: H7 hemagglutinin

SupramoleculeName: H7 hemagglutinin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: antibody 6Y13

SupramoleculeName: antibody 6Y13 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2

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Macromolecule #1: Hemagglutinin

MacromoleculeName: Hemagglutinin / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Influenza A virus (A/duck/Chiba/25-51-14/2013(H7N1))
Strain: A/duck/Chiba/25-51-14/2013(H7N1)
Molecular weightTheoretical: 56.382941 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: DKICLGHHAV SNGTKVNTLT ERGVEVVNAT ETVERTNVPR ICSKGKRTVD LGQCGLLGTI TGPPQCDQFL EFSADLIIER REGSDVCYP GKFVNEEALR QILRESGGID KETMGFTYSG IRTNGATSAC RRSGSSFYAE MKWLLSNTDN AAFPQMTKSY K NTRRDPAL ...String:
DKICLGHHAV SNGTKVNTLT ERGVEVVNAT ETVERTNVPR ICSKGKRTVD LGQCGLLGTI TGPPQCDQFL EFSADLIIER REGSDVCYP GKFVNEEALR QILRESGGID KETMGFTYSG IRTNGATSAC RRSGSSFYAE MKWLLSNTDN AAFPQMTKSY K NTRRDPAL IVWGIHHSGS TTEQTKLYGS GSKLITVGSS NYQQSFVPSP GARPQVNGQS GRIDFHWLIL NPNDTVTFSF NG AFIAPDR ASFLRGKSMG IQSGVQVDAN CEGDCYHSGG TIISNLPFQN INSRAVGKCP RYVKQESLML ATGMKNVPEL PKG RGLFGA IAGFIENGWE GLIDGWYGFR HQNAQGEGTA ADYKSTQSAI DQITGKLNRL IEKTNQQFEL IDNEFTEVEK QIGN VINWT RDSMTEVWSY NAELLVAMEN QHTIDLADSE MNKLYERVRR QLRENAEEDG TGCFEIFHKC DDDCMASIRN NTYDH SKYR EEAMQNRIQI DPVKEFRLVP R

UniProtKB: Hemagglutinin

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Macromolecule #2: scFv of 6Y13 chimera

MacromoleculeName: scFv of 6Y13 chimera / type: protein_or_peptide / ID: 2 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.301318 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIVMTQSPDS LAVSLGERAT INCKSSQSVL SGSINMNYLA WYQQKPGQPP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT VSSLQAEDV AVYYCQQYYS TPLTFGGGTK VEIKGGGGSG GGGSGGGGSQ VQLVESGGGV VQPGRSLRLS CAASGFSFSN Y GLHWVRQA ...String:
DIVMTQSPDS LAVSLGERAT INCKSSQSVL SGSINMNYLA WYQQKPGQPP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT VSSLQAEDV AVYYCQQYYS TPLTFGGGTK VEIKGGGGSG GGGSGGGGSQ VQLVESGGGV VQPGRSLRLS CAASGFSFSN Y GLHWVRQA PGKGLDWVAV ISYDGTNKYY ADSVKGRFTI SRDNSKNTLH LQMNSLRAED TAVYYCAKGR GPYCSSSICY HG MDVWGQG TTVTVSSHHH HHHHHHH

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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: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 83312
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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