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- PDB-6xsk: Cryo-EM Structure of Vaccine-Elicited Rhesus Antibody 789-203-3C1... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6xsk | |||||||||
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Title | Cryo-EM Structure of Vaccine-Elicited Rhesus Antibody 789-203-3C12 in Complex with Stabilized SI06 (A/Solomon Islands/3/06) Influenza Hemagglutinin Trimer | |||||||||
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![]() | IMMUNE SYSTEM/Viral Protein / Hemagglutinin ectodomain / Prefusion conformation / Vaccine-elicited antibody / Disulfide-stabilized trimer / IMMUNE SYSTEM / IMMUNE SYSTEM-Viral Protein 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.85 Å | |||||||||
![]() | Cerutti, G. / Gorman, J. / Kwong, P.D. / Shapiro, L. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses. Authors: Syed M Moin / Jeffrey C Boyington / Seyhan Boyoglu-Barnum / Rebecca A Gillespie / Gabriele Cerutti / Crystal Sao-Fong Cheung / Alberto Cagigi / John R Gallagher / Joshua Brand / Madhu ...Authors: Syed M Moin / Jeffrey C Boyington / Seyhan Boyoglu-Barnum / Rebecca A Gillespie / Gabriele Cerutti / Crystal Sao-Fong Cheung / Alberto Cagigi / John R Gallagher / Joshua Brand / Madhu Prabhakaran / Yaroslav Tsybovsky / Tyler Stephens / Brian E Fisher / Adrian Creanga / Sila Ataca / Reda Rawi / Kizzmekia S Corbett / Michelle C Crank / Gunilla B Karlsson Hedestam / Jason Gorman / Adrian B McDermott / Audray K Harris / Tongqing Zhou / Peter D Kwong / Lawrence Shapiro / John R Mascola / Barney S Graham / Masaru Kanekiyo / ![]() ![]() Abstract: Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA ...Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA stem harbors a supersite that is targeted by broadly neutralizing antibodies (bnAbs), representing a prime target for universal vaccines. Here, we showed that the co-immunization of two HA stem immunogens derived from group 1 and 2 influenza A viruses elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and protected against diverse viruses, including H5N1 and H7N9. Genetic and structural analyses revealed strong homology between macaque and human bnAbs, illustrating common biophysical constraints for acquiring cross-group specificity. Vaccine elicitation of stem-directed cross-group-protective immunity represents a step toward the development of broadly protective influenza vaccines. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 405.9 KB | Display | ![]() |
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PDB format | ![]() | 325.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.1 MB | Display | ![]() |
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Full document | ![]() | 2.1 MB | Display | |
Data in XML | ![]() | 68.8 KB | Display | |
Data in CIF | ![]() | 101.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22302MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Hemagglutinin ... , 2 types, 6 molecules ACEBDF
#3: Protein | Mass: 38269.184 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Solomon Islands/3/2006(H1N1) / Gene: HA / Production host: ![]() #4: Protein | Mass: 25264.090 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Strain: A/Solomon Islands/3/2006(H1N1) / Gene: HA / Production host: ![]() |
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-Antibody , 2 types, 6 molecules LJKHGI
#1: Antibody | Mass: 23209.664 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Antibody | Mass: 49298.629 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars , 3 types, 24 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.85 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 116041 / Symmetry type: POINT | |||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT | |||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6FYT |