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Yorodumi- PDB-6xsk: Cryo-EM Structure of Vaccine-Elicited Rhesus Antibody 789-203-3C1... -
+Open data
-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 | |||||||||
Components |
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Keywords | IMMUNE SYSTEM/Viral Protein / Hemagglutinin ectodomain / Prefusion conformation / Vaccine-elicited antibody / Disulfide-stabilized trimer / IMMUNE SYSTEM / IMMUNE SYSTEM-Viral Protein 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 | |||||||||
Biological species | Macaca mulatta (Rhesus monkey) Influenza A virus | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.85 Å | |||||||||
Authors | Cerutti, G. / Gorman, J. / Kwong, P.D. / Shapiro, L. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Immunity / Year: 2022 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6xsk.cif.gz | 405.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xsk.ent.gz | 325.8 KB | Display | PDB format |
PDBx/mmJSON format | 6xsk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xs/6xsk ftp://data.pdbj.org/pub/pdb/validation_reports/xs/6xsk | HTTPS FTP |
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-Related structure data
Related structure data | 22302MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Influenza A virus (A/Solomon Islands/3/2006(H1N1)) Strain: A/Solomon Islands/3/2006(H1N1) / Gene: HA / Production host: Homo sapiens (human) / References: UniProt: A7Y8I1 #4: Protein | Mass: 25264.090 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus (A/Solomon Islands/3/2006(H1N1)) Strain: A/Solomon Islands/3/2006(H1N1) / Gene: HA / Production host: Homo sapiens (human) / References: UniProt: A7Y8I1 |
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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.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) #2: Antibody | Mass: 49298.629 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) |
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-Sugars , 3 types, 24 molecules
#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 |
-Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-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 |