Journal: Cell Rep / Year: 2018 Title: Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design. Authors: Kimmo Rantalainen / Zachary T Berndsen / Sasha Murrell / Liwei Cao / Oluwarotimi Omorodion / Jonathan L Torres / Mengyu Wu / Jeffrey Umotoy / Jeffrey Copps / Pascal Poignard / Elise Landais / James C Paulson / Ian A Wilson / Andrew B Ward Abstract: Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at ...Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes. Additionally, we observed differences in site-specific glycosylation between soluble and full-length Env constructs, which may be important for tuning optimal immunogenicity in soluble Env trimers. These studies therefore provide important guideposts for design of immunogens that prime and mature nAb responses to the Env V2-apex.
Date
Deposition: May 9, 2018 / Header (metadata) release: May 30, 2018 / Map release: Jun 27, 2018 / Last update: Jun 27, 2018
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Structure visualization
Movie
Surface view with section colored by density value
Name: HIV-1 Envelope Glycoprotein clone PC64M4C054.SOSIP.664.N130A Recombinant expression: No
Source
Species: Human immunodeficiency virus 1
Source (engineered)
Expression System: Homo sapiens (human)
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Component #3: protein, Immunoglobulin G PCT64-13C Fab, Heavy chain
Protein
Name: Immunoglobulin G PCT64-13C Fab, Heavy chain / Recombinant expression: No
Source
Species: Homo sapiens (human)
Source (engineered)
Expression System: Homo sapiens (human)
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Component #4: protein, Immunoglobulin G PCT64-13C Fab, Light chain
Protein
Name: Immunoglobulin G PCT64-13C Fab, Light chain / Recombinant expression: No
Source
Species: Homo sapiens (human)
Source (engineered)
Expression System: Homo sapiens (human)
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Experimental details
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Sample preparation
Specimen
Specimen state: particle
Sample solution
pH: 7.4
Vitrification
Cryogen name: NONE
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Electron microscopy imaging
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company
Imaging
Microscope: FEI TECNAI SPIRIT
Electron gun
Electron source: LAB6 / Accelerating voltage: 120 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM
Lens
Imaging mode: BRIGHT FIELD
Specimen Holder
Model: OTHER
Camera
Detector: TVIPS TEMCAM-F416 (4k x 4k)
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Image acquisition
Image acquisition
Number of digital images: 222
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Image processing
Processing
Method: single particle reconstruction / Applied symmetry: C1 (asymmetric) / Number of projections: 2395
3D reconstruction
Resolution: 3 Å / Resolution method: FSC 0.5 CUT-OFF
FSC plot (resolution estimation)
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