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- PDB-7t3d: CryoEM map of anchor 222-1C06 Fab and lateral patch 2B05 Fab bind... -

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Basic information

Entry
Database: PDB / ID: 7t3d
TitleCryoEM map of anchor 222-1C06 Fab and lateral patch 2B05 Fab binding H1 HA
Components
  • (222-1C06 mAb ...) x 2
  • (Hemagglutinin ...) x 2
  • 2B05 mAb heavy chain
  • 2B05 mAb light chain
KeywordsViral Protein/IMMUNE SYSTEM / anchor / antibodies / influenza A virus / hemagglutinin / IMMUNE SYSTEM / 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
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
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.38 Å
AuthorsHan, J. / Ward, A.B.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)75N93019C00051 United States
CitationJournal: Nature / Year: 2022
Title: Broadly neutralizing antibodies target a haemagglutinin anchor epitope.
Authors: Jenna J Guthmiller / Julianna Han / Henry A Utset / Lei Li / Linda Yu-Ling Lan / Carole Henry / Christopher T Stamper / Meagan McMahon / George O'Dell / Monica L Fernández-Quintero / Alec W ...Authors: Jenna J Guthmiller / Julianna Han / Henry A Utset / Lei Li / Linda Yu-Ling Lan / Carole Henry / Christopher T Stamper / Meagan McMahon / George O'Dell / Monica L Fernández-Quintero / Alec W Freyn / Fatima Amanat / Olivia Stovicek / Lauren Gentles / Sara T Richey / Alba Torrents de la Peña / Victoria Rosado / Haley L Dugan / Nai-Ying Zheng / Micah E Tepora / Dalia J Bitar / Siriruk Changrob / Shirin Strohmeier / Min Huang / Adolfo García-Sastre / Klaus R Liedl / Jesse D Bloom / Raffael Nachbagauer / Peter Palese / Florian Krammer / Lynda Coughlan / Andrew B Ward / Patrick C Wilson /
Abstract: Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection. However, viral ...Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection. However, viral mutants that escape broadly neutralizing antibodies have been reported. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.
History
DepositionDec 7, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 12, 2022Provider: repository / Type: Initial release
Revision 1.1Feb 23, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation.year / _citation_author.identifier_ORCID
Revision 1.2Mar 30, 2022Group: Data processing / Category: em_3d_reconstruction / Item: _em_3d_reconstruction.resolution

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Assembly

Deposited unit
A: Hemagglutinin HA1 chain
B: Hemagglutinin HA2 chain
D: 2B05 mAb light chain
C: 2B05 mAb heavy chain
H: 222-1C06 mAb heavy chain
L: 222-1C06 mAb light chain
E: Hemagglutinin HA1 chain
G: Hemagglutinin HA2 chain
M: 2B05 mAb light chain
J: 2B05 mAb heavy chain
O: 222-1C06 mAb heavy chain
Q: 222-1C06 mAb light chain
F: Hemagglutinin HA1 chain
I: Hemagglutinin HA2 chain
N: 2B05 mAb light chain
K: 2B05 mAb heavy chain
P: 222-1C06 mAb heavy chain
R: 222-1C06 mAb light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)323,98936
Polymers319,39818
Non-polymers4,59118
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Hemagglutinin ... , 2 types, 6 molecules AEFBGI

#1: Protein Hemagglutinin HA1 chain


Mass: 36729.402 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Influenza A virus (A/California/04/2009(H1N1))
Strain: swl A/California/04/2009 H1N1 / Gene: HA / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: C3W5S1
#2: Protein Hemagglutinin HA2 chain


Mass: 19977.125 Da / Num. of mol.: 3 / Mutation: E47K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Influenza A virus (A/California/04/2009(H1N1))
Strain: swl A/California/04/2009 H1N1 / Gene: HA / Cell line (production host): 293F / Production host: Homo sapiens (human) / References: UniProt: C3W5S1

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Antibody , 4 types, 12 molecules DMNCJKHOPLQR

#3: Antibody 2B05 mAb light chain


Mass: 11769.120 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#4: Antibody 2B05 mAb heavy chain


Mass: 12805.238 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#5: Antibody 222-1C06 mAb heavy chain


Mass: 13528.006 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#6: Antibody 222-1C06 mAb light chain


Mass: 11657.012 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)

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Sugars , 2 types, 18 molecules

#7: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#8: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 15 / Source method: obtained synthetically / Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Details

Has ligand of interestY

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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

Component
IDNameTypeEntity IDParent-IDSource
1CryoEM map of anchor 222-1C06 Fab and lateral patch 2B05 Fab binding H1 HACOMPLEX#1-#60RECOMBINANT
2Monoclonal antibodies 222-1C06 and 2B05COMPLEX#3-#61RECOMBINANT
3HemagglutininCOMPLEX#1-#21RECOMBINANT
Molecular weight
IDEntity assembly-IDExperimental value
11NO
21NO
31NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
32Homo sapiens (human)9606
43Influenza A virus (A/California/04/2009(H1N1))641501
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
21Homo sapiens (human)9606293F
32Homo sapiens (human)9606293F
43Homo sapiens (human)9606293F
Buffer solutionpH: 7.4 / Details: Tris-buffered saline
SpecimenConc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm
Image recordingElectron dose: 49.9 e/Å2 / Film or detector model: TVIPS TEMCAM-F416 (4k x 4k)

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Processing

EM software
IDNameVersionCategory
2Leginonimage acquisition
13cryoSPARC23D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 48846 / Symmetry type: POINT

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