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- PDB-9e6j: DH726-1 Fab bound to hemagglutinin from influenza A/Solomon Islan... -

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Basic information

Entry
Database: PDB / ID: 9e6j
TitleDH726-1 Fab bound to hemagglutinin from influenza A/Solomon Islands/3/2006
Components
  • DH726-1 Fab heavy chain
  • DH726-1 Fab light chain
  • Hemagglutinin
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / immunoglobulin / antibody / 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 / 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 speciesAlphainfluenzavirus influenzae
Macaca mulatta (Rhesus monkey)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.98 Å
AuthorsFinney, J. / Harrison, S.C.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI089618 United States
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: bioRxiv / Year: 2026
Title: Elicitation of stem-directed antibodies in rhesus macaques by a conventional hemagglutinin immunogen.
Authors: Shuqin Gu / Joel Finney / Kan Luo / Sarah M Valencia / Dieter Mielke / Tarra A Von Holle / Dawn J Marshall / Robert Parks / Laura L Sutherland / Richard M Scearce / Kevin Wiehe / Sampa ...Authors: Shuqin Gu / Joel Finney / Kan Luo / Sarah M Valencia / Dieter Mielke / Tarra A Von Holle / Dawn J Marshall / Robert Parks / Laura L Sutherland / Richard M Scearce / Kevin Wiehe / Sampa Santra / Summer Harris / Jacquelyn DuVall / Chelsea D Landon / M Ariel Spurrier / Nicholas S Heaton / Hadi M Yassine / Barney S Graham / Thomas B Kepler / Hua-Xin Liao / Aaron G Schmidt / Guido Ferrari / Barton F Haynes / Stephen C Harrison / M Anthony Moody /
Abstract: Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at ...Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.
History
DepositionOct 30, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 21, 2026Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Hemagglutinin
H: DH726-1 Fab heavy chain
L: DH726-1 Fab light chain
B: Hemagglutinin
I: DH726-1 Fab heavy chain
M: DH726-1 Fab light chain
C: Hemagglutinin
J: DH726-1 Fab heavy chain
N: DH726-1 Fab light chain


Theoretical massNumber of molelcules
Total (without water)321,3299
Polymers321,3299
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Hemagglutinin


Mass: 58436.199 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Alphainfluenzavirus influenzae / Strain: A/Solomon Islands/3/2006 / Gene: HA / Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: A7UPX0
#2: Antibody DH726-1 Fab heavy chain


Mass: 25467.539 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): Expi293 / Production host: Homo sapiens (human)
#3: Antibody DH726-1 Fab light chain


Mass: 23205.787 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): High Five / Production host: Homo sapiens (human)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Complex of three DH726-1 Fabs with homotrimeric hemagglutinin
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Alphainfluenzavirus influenzae / Strain: A/Solomon Islands/3/2006
Source (recombinant)Organism: Trichoplusia ni (cabbage looper) / Strain: High Five
Buffer solutionpH: 7.4
SpecimenConc.: 1.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE

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Electron microscopy imaging

MicroscopyModel: TFS TALOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 36000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 49.99 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
7UCSF ChimeraX1.8model fitting
8Coot0.9.8.91model fitting
10PHENIX1.21.1_5286model refinement
11Coot0.9.8.91model refinement
15cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C3 (3 fold cyclic)
3D reconstructionResolution: 2.98 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 180435 / Symmetry type: POINT
Atomic model building
IDPDB-ID 3D fitting-IDAccession codeSource nameType
15UGY

5ugy

15UGYPDBexperimental model
26XSK

6xsk

16XSKPDBexperimental model

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