+Open data
-Basic information
Entry | Database: PDB / ID: 8vuz | ||||||
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Title | L5A7 Fab bound to 28H6E11 anti-idiotype Fab | ||||||
Components |
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Keywords | ANTIVIRAL PROTEIN / influenza / antibody / anti-idiotype | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.95 Å | ||||||
Authors | Olia, A.S. / Morano, N.C. / Kwong, P.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: Front Immunol / Year: 2024 Title: Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody. Authors: Adam S Olia / Madhu Prabhakaran / Darcy R Harris / Crystal Sao-Fong Cheung / Rebecca A Gillespie / Jason Gorman / Abigayle Hoover / Nicholas C Morano / Amine Ourahmane / Abhinaya Srikanth / ...Authors: Adam S Olia / Madhu Prabhakaran / Darcy R Harris / Crystal Sao-Fong Cheung / Rebecca A Gillespie / Jason Gorman / Abigayle Hoover / Nicholas C Morano / Amine Ourahmane / Abhinaya Srikanth / Shuishu Wang / Weiwei Wu / Tongqing Zhou / Sarah F Andrews / Masaru Kanekiyo / Lawrence Shapiro / Adrian B McDermott / Peter D Kwong / Abstract: The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline ...The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8vuz.cif.gz | 160.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8vuz.ent.gz | 124.4 KB | Display | PDB format |
PDBx/mmJSON format | 8vuz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8vuz_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8vuz_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8vuz_validation.xml.gz | 36.4 KB | Display | |
Data in CIF | 8vuz_validation.cif.gz | 52.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vu/8vuz ftp://data.pdbj.org/pub/pdb/validation_reports/vu/8vuz | HTTPS FTP |
-Related structure data
Related structure data | 43545MC 8vueC 8vvbC C: citing same article (ref.) M: map data used to model this data |
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-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Antibody | Mass: 23499.348 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 24146.812 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 24642.494 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#4: Antibody | Mass: 22716.301 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complex of L5A7 Fab and 28H6E11 Fab / Type: COMPLEX / Entity ID: #3-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2 mg/ml / 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: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 215254 / Symmetry type: POINT | ||||||||||||||||||||||||
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