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- EMDB-22385: Rh137.3 monoclonal complexed with BG505v3 trimer -

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Basic information

Entry
Database: EMDB / ID: EMD-22385
TitleRh137.3 monoclonal complexed with BG505v3 trimer
Map data
Sample
  • Complex: Rh137.3 monoclonal complexed with BG505v3 trimer
Biological speciesMacaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / negative staining / Resolution: 27.1 Å
AuthorsNogal B / Cottrell CA / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI144462 United States
Bill & Melinda Gates FoundationOPP1196345/INV-008813 United States
CitationJournal: Cell Rep / Year: 2020
Title: Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques.
Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / ...Authors: Fangzhu Zhao / Collin Joyce / Alison Burns / Bartek Nogal / Christopher A Cottrell / Alejandra Ramos / Trevor Biddle / Matthias Pauthner / Rebecca Nedellec / Huma Qureshi / Rosemarie Mason / Elise Landais / Bryan Briney / Andrew B Ward / Dennis R Burton / Devin Sok /
Abstract: BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs) ...BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a "public clonotype" that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.
History
DepositionJul 31, 2020-
Header (metadata) releaseSep 23, 2020-
Map releaseSep 23, 2020-
UpdateSep 23, 2020-
Current statusSep 23, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.012
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.012
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22385.png

Downloads & links

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Map

FileDownload / File: emd_22385.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.98 Å
Density
Contour LevelBy AUTHOR: 0.012 / Movie #1: 0.012
Minimum - Maximum-0.041031916 - 0.104795
Average (Standard dev.)0.0000617403 (±0.0042984225)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 380.16 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.981.981.98
M x/y/z192192192
origin x/y/z0.0000.0000.000
length x/y/z380.160380.160380.160
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ400400400
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS192192192
D min/max/mean-0.0410.1050.000

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Supplemental data

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Sample components

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Entire : Rh137.3 monoclonal complexed with BG505v3 trimer

EntireName: Rh137.3 monoclonal complexed with BG505v3 trimer
Components
  • Complex: Rh137.3 monoclonal complexed with BG505v3 trimer

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Supramolecule #1: Rh137.3 monoclonal complexed with BG505v3 trimer

SupramoleculeName: Rh137.3 monoclonal complexed with BG505v3 trimer / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Recombinant expressionOrganism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 5.5
StainingType: NEGATIVE / Material: uranyl formate
GridDetails: unspecified

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Electron microscopy

MicroscopeFEI TECNAI 12
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: OTHER / Average electron dose: 25.0 e/Å2

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Image processing

Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 27.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 8326

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