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- EMDB-20269: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B -

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Basic information

Entry
Database: EMDB / ID: EMD-20269
TitleChikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
Map dataChikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
Sample
  • Complex: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
    • Complex: Fab from IgG DC2.271B
    • Complex: Chikungunya virus p62/E1
Biological speciesHomo sapiens (human) / Chikungunya virus
Methodsingle particle reconstruction / negative staining / Resolution: 24.0 Å
AuthorsPallesen J / Ward AB
CitationJournal: PLoS Pathog / Year: 2019
Title: Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins.
Authors: Jose A Quiroz / Ryan J Malonis / Larissa B Thackray / Courtney A Cohen / Jesper Pallesen / Rohit K Jangra / Rebecca S Brown / Daniel Hofmann / Frederick W Holtsberg / Sergey Shulenin / ...Authors: Jose A Quiroz / Ryan J Malonis / Larissa B Thackray / Courtney A Cohen / Jesper Pallesen / Rohit K Jangra / Rebecca S Brown / Daniel Hofmann / Frederick W Holtsberg / Sergey Shulenin / Elisabeth K Nyakatura / Lorellin A Durnell / Vinayak Rayannavar / Johanna P Daily / Andrew B Ward / M Javad Aman / John M Dye / Kartik Chandran / Michael S Diamond / Margaret Kielian / Jonathan R Lai /
Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal ...Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.
History
DepositionJun 6, 2019-
Header (metadata) releaseJul 17, 2019-
Map releaseNov 20, 2019-
UpdateNov 20, 2019-
Current statusNov 20, 2019Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.04
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.04
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_20269.png

Downloads & links

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Map

FileDownload / File: emd_20269.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationChikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
5.08 Å/pix.
x 128 pix.
= 650.24 Å		5.08 Å/pix.
x 128 pix.
= 650.24 Å		5.08 Å/pix.
x 128 pix.
= 650.24 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 5.08 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.04 / Movie #1: 0.04
Minimum - Maximum-0.08097774 - 0.20212354
Average (Standard dev.)0.0000612826 (±0.0035655422)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 650.24 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z5.085.085.08
M x/y/z128128128
origin x/y/z0.0000.0000.000
length x/y/z650.240650.240650.240
α/β/γ90.00090.00090.000
start NX/NY/NZ929262
NX/NY/NZ290290360
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS128128128
D min/max/mean-0.0810.2020.000

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Supplemental data

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Half map: Chikungunya virus p62/E1 in complex with Fab from...

Fileemd_20269_half_map_1.map
AnnotationChikungunya virus p62/E1 in complex with Fab from IgG DC2.271B, half map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Chikungunya virus p62/E1 in complex with Fab from...

Fileemd_20269_half_map_2.map
AnnotationChikungunya virus p62/E1 in complex with Fab from IgG DC2.271B, half map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B

EntireName: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
Components
  • Complex: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
    • Complex: Fab from IgG DC2.271B
    • Complex: Chikungunya virus p62/E1

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Supramolecule #1: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B

SupramoleculeName: Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
type: complex / ID: 1 / Parent: 0
Molecular weightTheoretical: 85 KDa

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Supramolecule #2: Fab from IgG DC2.271B

SupramoleculeName: Fab from IgG DC2.271B / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: Chikungunya virus p62/E1

SupramoleculeName: Chikungunya virus p62/E1 / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Chikungunya virus
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: 7
StainingType: NEGATIVE / Material: uranyl formate
GridDetails: unspecified

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: FEI CETA (4k x 4k) / Average electron dose: 30.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 57000
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: Gctf
Startup modelType of model: OTHER
Details: negative stain reconstruction of chikungunya virus p62/E1
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 24.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION / Number images used: 27196
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
FSC plot (resolution estimation)

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