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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
Sample
  • Complex: Chimpanzee SIV Env trimeric ectodomain.
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp160
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Function / homology
Function and homology information


membrane fusion involved in viral entry into host cell / host cell endosome membrane / membrane => GO:0016020 / viral envelope / structural molecule activity / virion attachment to host cell / host cell plasma membrane / virion membrane / plasma membrane
Similarity search - Function
Retroviral envelope protein / Retroviral envelope protein GP41-like / Gp120 core superfamily / Envelope glycoprotein GP120 / Human immunodeficiency virus 1, envelope glycoprotein Gp120
Similarity search - Domain/homology
Envelope glycoprotein gp160
Similarity search - Component
Biological speciesSimian immunodeficiency virus
Methodsingle particle reconstruction / cryo EM / Resolution: 4.1 Å
AuthorsPallesen J / Andrabi R / de Val N / Burton DR / Ward AB
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI100663 United States
Bill & Melinda Gates FoundationOPP1084519 United States
Bill & Melinda Gates FoundationOPP115782 United States
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- ...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.
History
DepositionApr 8, 2019-
Header (metadata) releaseJun 5, 2019-
Map releaseJun 5, 2019-
UpdateJul 29, 2020-
Current statusJul 29, 2020Processing site: RCSB / Status: Released

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Structure visualization

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

emd_20074.png

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)
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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Half map: #1

Fileemd_20074_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_20074_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Chimpanzee SIV Env trimeric ectodomain.

EntireName: Chimpanzee SIV Env trimeric ectodomain.
Components
  • Complex: Chimpanzee SIV Env trimeric ectodomain.
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: Envelope glycoprotein gp160
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Chimpanzee SIV Env trimeric ectodomain.

SupramoleculeName: Chimpanzee SIV Env trimeric ectodomain. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Simian immunodeficiency virus
Recombinant expressionOrganism: Homo sapiens (human)
Molecular weightTheoretical: 450 KDa

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Macromolecule #1: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Simian immunodeficiency virus
Molecular weightTheoretical: 51.708664 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ENWWVTVYYG VPVWREAKTT LFCASDAKSY STEAHNIWAT QACVPTDPTP QEVLLPNVTE EFNMWENYMV DQMQEDIISL WEQSLKPCV KLTPLCVTLT CNNPTNTSCT NSTDDRLGDM RNCSFNVTTE LRDKKRKVYS LFYVEDITAI GNNSTYRLIN C NTTAITQA ...String:
ENWWVTVYYG VPVWREAKTT LFCASDAKSY STEAHNIWAT QACVPTDPTP QEVLLPNVTE EFNMWENYMV DQMQEDIISL WEQSLKPCV KLTPLCVTLT CNNPTNTSCT NSTDDRLGDM RNCSFNVTTE LRDKKRKVYS LFYVEDITAI GNNSTYRLIN C NTTAITQA CPKTSFEPIP IHYCAPAGFA LLKCNDIDYK GNETCKNVST VHCTHGIKPV ATTQLILNGS TADNQTVARI DP SENLAII QLKDPVKITC RRPGNNTRGQ IQIGPAMTFY NIENVVGDTR KAYCEINGTQ WAKALNETKE VLRNILRKNI SFM VPSGGD PEVTNHHFNC GGEFFYCNTS EIINITKINK TENMTIIPCR IRQIVNSWMR VGKGIFAPPI RGNITCTSNI TGML LEIHK NREDQGEDQD QNNTYVCLTG GNMKDIWRSE LYKYKIVEIQ PLGVAPTKCR RY

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Macromolecule #2: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Simian immunodeficiency virus
Molecular weightTheoretical: 17.17949 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
LGALFLGFLG AAGSTMGAAS VVLTVQARQL LTGIVQQQNN LLRAPEAQQH LLQLSVWGIK QLQARVLAVE RYLRDQQLLG LWGCTGKTI CCTAVRWNKT WGNISDYQVI WNNYTWQQWD REVNNYTGLI YTLLEEANTQ QEKNEKELLE LD

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Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 24 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 10.0 sec. / Average electron dose: 94.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: Gctf
Startup modelType of model: EMDB MAP
EMDB ID:

8714

Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final 3D classificationNumber classes: 6 / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 44301
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

4tvp

RefinementSpace: REAL / Protocol: OTHER
Output model

PDB-6ohy:
Chimpanzee SIV Env trimeric ectodomain.

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