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Yorodumi- EMDB-29334: N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at d... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29334 | |||||||||
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Title | N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at day 16 from mRNA immunized wild type mice | |||||||||
Map data | day 16 V1V3 response main map | |||||||||
Sample |
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Keywords | polyclonal antibodies / mouse antibody / germline targeting / HIV-1 / vaccine design / VIRAL PROTEIN | |||||||||
Biological species | Mus musculus (house mouse) / Human immunodeficiency virus | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 25.0 Å | |||||||||
Authors | Torres JL / Jackson AM / Ozorowski G / Ward AB | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Science / Year: 2024 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_29334.map.gz | 20.6 MB | EMDB map data format | |
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Header (meta data) | emd-29334-v30.xml emd-29334.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
Images | emd_29334.png | 41.4 KB | ||
Filedesc metadata | emd-29334.cif.gz | 4.5 KB | ||
Others | emd_29334_half_map_1.map.gz emd_29334_half_map_2.map.gz | 20.6 MB 20.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29334 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29334 | HTTPS FTP |
-Validation report
Summary document | emd_29334_validation.pdf.gz | 661.3 KB | Display | EMDB validaton report |
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Full document | emd_29334_full_validation.pdf.gz | 660.8 KB | Display | |
Data in XML | emd_29334_validation.xml.gz | 10.7 KB | Display | |
Data in CIF | emd_29334_validation.cif.gz | 12.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29334 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29334 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_29334.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | day 16 V1V3 response main map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: day 16 V1V3 response half map A
File | emd_29334_half_map_1.map | ||||||||||||
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Annotation | day 16 V1V3 response half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: day 16 V1V3 response half map B
File | emd_29334_half_map_2.map | ||||||||||||
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Annotation | day 16 V1V3 response half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at d...
Entire | Name: N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at day 16 from mRNA immunized wild type mice |
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Components |
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-Supramolecule #1: N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at d...
Supramolecule | Name: N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at day 16 from mRNA immunized wild type mice type: complex / ID: 1 / Parent: 0 |
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-Supramolecule #2: V1V3 polyclonal Fabs
Supramolecule | Name: V1V3 polyclonal Fabs / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Supramolecule #3: N332-GT5 SOSIP
Supramolecule | Name: N332-GT5 SOSIP / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Human immunodeficiency virus |
-Experimental details
-Structure determination
Method | negative staining |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.03 mg/mL |
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Buffer | pH: 7.4 |
Staining | Type: NEGATIVE / Material: uranyl formate |
-Electron microscopy
Microscope | FEI TECNAI SPIRIT |
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Image recording | Film or detector model: FEI EAGLE (2k x 2k) / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 120 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Tecnai Spirit / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: PDB coordinates converted to map using UCSF Chimera molmap and low pass filtered to 40 Angstrom |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 5410 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |