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- EMDB-23488: Hendra virus receptor binding protein in complex with HENV-103 an... -

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Basic information

Entry
Database: EMDB / ID: EMD-23488
TitleHendra virus receptor binding protein in complex with HENV-103 and HENV-117 Fabs
Map data
Sample
  • Complex: HeV RBP with 2 Fabs
Biological speciesHendra henipavirus
Methodsingle particle reconstruction / negative staining / Resolution: 15.0 Å
AuthorsBinshtein E / Crowe JE
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS)U19 AI142764 United States
CitationJournal: Cell Rep / Year: 2021
Title: Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein.
Authors: Michael P Doyle / Nurgun Kose / Viktoriya Borisevich / Elad Binshtein / Moushimi Amaya / Marcus Nagel / Edward J Annand / Erica Armstrong / Robin Bombardi / Jinhui Dong / Kevin L Schey / ...Authors: Michael P Doyle / Nurgun Kose / Viktoriya Borisevich / Elad Binshtein / Moushimi Amaya / Marcus Nagel / Edward J Annand / Erica Armstrong / Robin Bombardi / Jinhui Dong / Kevin L Schey / Christopher C Broder / Larry Zeitlin / Erin A Kuang / Zachary A Bornholdt / Brandyn R West / Thomas W Geisbert / Robert W Cross / James E Crowe /
Abstract: Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a ...Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. The most potent class of cross-reactive antibodies achieves neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3, with a second class being enhanced by receptor binding. mAbs from both classes display synergistic activity in vitro. In a stringent hamster model of NiV Bangladesh (NiV) infection, antibodies from both classes reduce morbidity and mortality and achieve synergistic protection in combination. These candidate mAbs might be suitable for use in a cocktail therapeutic approach to achieve synergistic potency and reduce the risk of virus escape.
History
DepositionFeb 15, 2021-
Header (metadata) releaseJan 12, 2022-
Map releaseJan 12, 2022-
UpdateJan 12, 2022-
Current statusJan 12, 2022Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 4.2
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 4.2
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_23488.png

Downloads & links

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Map

FileDownload / File: emd_23488.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 3.514 Å
Density
Contour LevelBy AUTHOR: 4.2 / Movie #1: 4.2
Minimum - Maximum-3.006904 - 10.55124
Average (Standard dev.)-0.0068327207 (±0.37793347)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 449.792 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z3.5143.5143.514
M x/y/z128128128
origin x/y/z0.0000.0000.000
length x/y/z449.792449.792449.792
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS128128128
D min/max/mean-3.00710.551-0.007

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Supplemental data

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Sample components

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Entire : HeV RBP with 2 Fabs

EntireName: HeV RBP with 2 Fabs
Components
  • Complex: HeV RBP with 2 Fabs

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Supramolecule #1: HeV RBP with 2 Fabs

SupramoleculeName: HeV RBP with 2 Fabs / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Hendra henipavirus
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: 7.5
StainingType: NEGATIVE / Material: Uranyl Formate
GridModel: Homemade / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE

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Electron microscopy

MicroscopeFEI TECNAI F20
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.2 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 62000
Image recordingFilm or detector model: GATAN ULTRASCAN 4000 (4k x 4k) / Number grids imaged: 1 / Number real images: 377 / Average exposure time: 1.0 sec. / Average electron dose: 35.0 e/Å2
Experimental equipment
Model: Tecnai F20 / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 16552
CTF correctionSoftware - Name: cryoSPARC (ver. 3.0)
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 15.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 13082

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