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- PDB-8sx3: 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fa... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8sx3 | |||||||||
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Title | 10E8-GT10.2 immunogen in complex with human Fab 10E8 and mouse Fab W6-10 | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / HIV / Germline targeting / MPER / broadly neutralizing antibody / vaccine design / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Biological species | ![]() ![]() synthetic construct (others) ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
![]() | Huang, J. / Ozorowski, G. / Ward, A.B. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Vaccination induces broadly neutralizing antibody precursors to HIV gp41. Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel ...Authors: Torben Schiffner / Ivy Phung / Rashmi Ray / Adriana Irimia / Ming Tian / Olivia Swanson / Jeong Hyun Lee / Chang-Chun D Lee / Ester Marina-Zárate / So Yeon Cho / Jiachen Huang / Gabriel Ozorowski / Patrick D Skog / Andreia M Serra / Kimmo Rantalainen / Joel D Allen / Sabyasachi Baboo / Oscar L Rodriguez / Sunny Himansu / Jianfu Zhou / Jonathan Hurtado / Claudia T Flynn / Katherine McKenney / Colin Havenar-Daughton / Swati Saha / Kaitlyn Shields / Steven Schultze / Melissa L Smith / Chi-Hui Liang / Laura Toy / Simone Pecetta / Ying-Cing Lin / Jordan R Willis / Fabian Sesterhenn / Daniel W Kulp / Xiaozhen Hu / Christopher A Cottrell / Xiaoya Zhou / Jennifer Ruiz / Xuesong Wang / Usha Nair / Kathrin H Kirsch / Hwei-Ling Cheng / Jillian Davis / Oleksandr Kalyuzhniy / Alessia Liguori / Jolene K Diedrich / Julia T Ngo / Vanessa Lewis / Nicole Phelps / Ryan D Tingle / Skye Spencer / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Saman Eskandarzadeh / Marc A Elsliger / Rama R Amara / Elise Landais / Bryan Briney / Dennis R Burton / Diane G Carnathan / Guido Silvestri / Corey T Watson / John R Yates / James C Paulson / Max Crispin / Gevorg Grigoryan / Andrew B Ward / Devin Sok / Frederick W Alt / Ian A Wilson / Facundo D Batista / Shane Crotty / William R Schief / ![]() ![]() ![]() Abstract: A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design ...A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 129.8 KB | Display | ![]() |
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PDB format | ![]() | 94.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 39.1 KB | Display | |
Data in CIF | ![]() | 55.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 40825MC ![]() 8tznC ![]() 8tzwC ![]() 8u03C ![]() 8u08C ![]() 8v2eC 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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1 |
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Components
-Antibody , 4 types, 4 molecules ABHL
#1: Antibody | Mass: 23974.010 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Antibody | Mass: 23417.891 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Antibody | Mass: 25175.193 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#5: Antibody | Mass: 22959.434 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein / Sugars , 2 types, 2 molecules C
#3: Protein | Mass: 21073.750 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() |
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#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 |
-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
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / 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 defocus max: 1500 nm / Nominal defocus min: 700 nm |
Image recording | Electron dose: 53 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 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56628 / Symmetry type: POINT |