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- EMDB-9402: BG505 SOSIPv4.1 with rabbit Fab 12N -

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Basic information

Entry
Database: EMDB / ID: EMD-9402
TitleBG505 SOSIPv4.1 with rabbit Fab 12N
Map dataBG505 SOSIP.v4.1 with 12N Fab
Sample
  • Complex: BG505 SOSIPv4.1 with rabbit Fab 12N
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsCottrell CA / Shin M / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious DiseasesAI110657 United States
National Institutes of Health/National Institute Of Allergy and Infectious DiseasesAI131873 United States
CitationJournal: Nat Commun / Year: 2017
Title: Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding.
Authors: Daniel W Kulp / Jon M Steichen / Matthias Pauthner / Xiaozhen Hu / Torben Schiffner / Alessia Liguori / Christopher A Cottrell / Colin Havenar-Daughton / Gabriel Ozorowski / Erik Georgeson / ...Authors: Daniel W Kulp / Jon M Steichen / Matthias Pauthner / Xiaozhen Hu / Torben Schiffner / Alessia Liguori / Christopher A Cottrell / Colin Havenar-Daughton / Gabriel Ozorowski / Erik Georgeson / Oleksandr Kalyuzhniy / Jordan R Willis / Michael Kubitz / Yumiko Adachi / Samantha M Reiss / Mia Shin / Natalia de Val / Andrew B Ward / Shane Crotty / Dennis R Burton / William R Schief /
Abstract: Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore ...Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity. In rabbit immunizations with native-like trimers of the 327c isolate, improved trimers suppress elicitation of V3-directed and tier-1 neutralizing antibodies and induce robust autologous tier-2 neutralization, unlike a first-generation trimer. The improved native-like trimers from diverse HIV isolates, and the design methods, have promise to assist in the development of a HIV vaccine.
History
DepositionJun 2, 2019-
Header (metadata) releaseAug 21, 2019-
Map releaseAug 21, 2019-
UpdateAug 21, 2019-
Current statusAug 21, 2019Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.016
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.016
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_9402.png

Downloads & links

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Map

FileDownload / File: emd_9402.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationBG505 SOSIP.v4.1 with 12N Fab
Voxel sizeX=Y=Z: 1.98 Å
Density
Contour LevelBy AUTHOR: 0.016 / Movie #1: 0.016
Minimum - Maximum-0.049224608 - 0.06670936
Average (Standard dev.)0.00021304941 (±0.004822589)
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
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS192192192
D min/max/mean-0.0490.0670.000

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Supplemental data

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Sample components

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Entire : BG505 SOSIPv4.1 with rabbit Fab 12N

EntireName: BG505 SOSIPv4.1 with rabbit Fab 12N
Components
  • Complex: BG505 SOSIPv4.1 with rabbit Fab 12N

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Supramolecule #1: BG505 SOSIPv4.1 with rabbit Fab 12N

SupramoleculeName: BG505 SOSIPv4.1 with rabbit Fab 12N / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human) / Recombinant cell: HEK293F

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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: 7.4
StainingType: NEGATIVE / Material: UF

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: FEI CETA (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION / Number images used: 4072
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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