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- PDB-8f9m: HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex w... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8f9m | |||||||||
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Title | HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized wild type mice, and NHP monoclonal Fab RM20A3 | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / mouse antibody / germline targeting / HIV-1 / vaccine design / polyclonal / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Biological species | synthetic construct (others)![]() ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
![]() | Ozorowski, G. / Ward, A.B. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / ...Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / Stephanie R Weldon / Gordon A Dale / Kathrin H Kirsch / Usha Nair / Sabyasachi Baboo / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Abigail M Jackson / Sara T Richey / Reid M Volk / Jeong Hyun Lee / Jolene K Diedrich / Thavaleak Prum / Samantha Falcone / Sunny Himansu / Andrea Carfi / John R Yates / James C Paulson / Devin Sok / Andrew B Ward / William R Schief / Facundo D Batista / ![]() Abstract: Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells ...Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 467.9 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28945MC ![]() 8f92C ![]() 8f9gC ![]() 8vfvC M: map data used to model this data C: citing same article ( |
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Links
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Assembly
Deposited unit | ![]()
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Components
-BG505 MD64 N332-GT5 ... , 2 types, 6 molecules AEFBGI
#1: Protein | Mass: 54236.801 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() #4: Protein | Mass: 18250.541 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() |
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-Antibody , 4 types, 8 molecules CJKDMNHL
#2: Antibody | Mass: 13511.111 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Antibody | Mass: 13508.800 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Antibody | | Mass: 9634.868 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #6: Antibody | | Mass: 9379.553 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Sugars , 3 types, 51 molecules ![](data/chem/img/NAG.gif)
#7: 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 #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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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
Component | Name: HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized wild type mice, and NHP monoclonal Fab RM20A3 Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 190000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 700 nm / Alignment procedure: COMA FREE |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | |||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11058 / Symmetry type: POINT | |||||||||||||||||||||||||
Refine LS restraints |
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