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- EMDB-20074: Chimpanzee SIV Env trimeric ectodomain. -

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Basic information

Entry
Database: EMDB / ID: EMD-20074
TitleChimpanzee SIV Env trimeric ectodomain.
Map data
SampleChimpanzee SIV Env trimeric ectodomain.:
(Envelope glycoprotein ...) x 2 / (ligand) x 4
Function / homology
Function and homology information


membrane fusion involved in viral entry into host cell / host cell endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / integral component of membrane
Retroviral envelope protein GP41-like / Human immunodeficiency virus 1, envelope glycoprotein Gp120 / Gp120 core superfamily / Envelope glycoprotein GP120 / Retroviral envelope protein
Envelope glycoprotein gp160
Biological speciesSimian immunodeficiency virus
Methodsingle particle reconstruction / cryo EM / Resolution: 4.1 Å
AuthorsPallesen J / Andrabi R / de Val N / Burton DR / Ward AB
CitationJournal: Cell Rep / Year: 2019
Title: The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template.
Authors: Raiees Andrabi / Jesper Pallesen / Joel D Allen / Ge Song / Jinsong Zhang / Natalia de Val / Gavin Gegg / Katelyn Porter / Ching-Yao Su / Matthias Pauthner / Amanda Newman / Hilary Bouton-Verville / Fernando Garces / Ian A Wilson / Max Crispin / Beatrice H Hahn / Barton F Haynes / Laurent Verkoczy / Andrew B Ward / Dennis R Burton /
Abstract: Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) ...Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.
Validation ReportPDB-ID: 6ohy

SummaryFull reportAbout validation report
DateDeposition: Apr 8, 2019 / Header (metadata) release: Jun 5, 2019 / Map release: Jun 5, 2019 / Update: Jun 5, 2019

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.05
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.05
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: : PDB-6ohy
  • Surface level: 0.05
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_20074.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.02 Å/pix.
x 280 pix.
= 285.6 Å
1.02 Å/pix.
x 280 pix.
= 285.6 Å
1.02 Å/pix.
x 280 pix.
= 285.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.02 Å
Density
Contour LevelBy AUTHOR: 0.05 / Movie #1: 0.05
Minimum - Maximum-0.10039165 - 0.22258005
Average (Standard dev.)0.0004769411 (±0.00810612)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 285.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.021.021.02
M x/y/z280280280
origin x/y/z0.0000.0000.000
length x/y/z285.600285.600285.600
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS280280280
D min/max/mean-0.1000.2230.000

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Supplemental data

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Sample components

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Entire Chimpanzee SIV Env trimeric ectodomain.

EntireName: Chimpanzee SIV Env trimeric ectodomain. / Number of components: 7

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Component #1: protein, Chimpanzee SIV Env trimeric ectodomain.

ProteinName: Chimpanzee SIV Env trimeric ectodomain. / Recombinant expression: No
MassTheoretical: 450 kDa
SourceSpecies: Simian immunodeficiency virus
Source (engineered)Expression System: Homo sapiens (human)

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Component #2: protein, Envelope glycoprotein gp160

ProteinName: Envelope glycoprotein gp160 / Number of Copies: 3 / Recombinant expression: No
MassTheoretical: 51.708664 kDa
SourceSpecies: Simian immunodeficiency virus
Source (engineered)Expression System: Homo sapiens (human)

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Component #3: protein, Envelope glycoprotein gp160

ProteinName: Envelope glycoprotein gp160 / Number of Copies: 3 / Recombinant expression: No
MassTheoretical: 17.17949 kDa
SourceSpecies: Simian immunodeficiency virus
Source (engineered)Expression System: Homo sapiens (human)

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Component #4: ligand, N-ACETYL-D-GLUCOSAMINE

LigandName: N-ACETYL-D-GLUCOSAMINEN-Acetylglucosamine / Number of Copies: 96 / Recombinant expression: No
MassTheoretical: 0.221208 kDa

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Component #5: ligand, ALPHA-L-FUCOSE

LigandName: ALPHA-L-FUCOSE / Number of Copies: 15 / Recombinant expression: No
MassTheoretical: 0.164156 kDa

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Component #6: ligand, BETA-D-MANNOSE

LigandName: BETA-D-MANNOSE / Number of Copies: 3 / Recombinant expression: No
MassTheoretical: 0.180156 kDa

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Component #7: ligand, ALPHA-D-MANNOSE

LigandName: ALPHA-D-MANNOSE / Number of Copies: 12 / Recombinant expression: No
MassTheoretical: 0.180156 kDa

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Experimental details

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Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
ImagingMicroscope: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 94 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD
Specimen HolderModel: OTHER
CameraDetector: GATAN K2 SUMMIT (4k x 4k)

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Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: C3 (3 fold cyclic) / Number of projections: 44301
3D reconstructionSoftware: RELION / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF
FSC plot (resolution estimation)

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Atomic model buiding

Modeling #1Refinement space: REAL
Input PDB model: 4TVP
Output model

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