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- EMDB-23470: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound) -

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Basic information

Entry
Database: EMDB / ID: EMD-23470
TitleSARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)
Map datarefined map
Sample
  • Complex: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)
    • Complex: SARS-CoV spike glycoprotein
    • Complex: Fab CV38-142
Function / homology
Function and homology information


Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / receptor-mediated virion attachment to host cell / endoplasmic reticulum-Golgi intermediate compartment / host cell surface receptor binding / endocytosis involved in viral entry into host cell ...Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / suppression by virus of host tetherin activity / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / receptor-mediated virion attachment to host cell / endoplasmic reticulum-Golgi intermediate compartment / host cell surface receptor binding / endocytosis involved in viral entry into host cell / endocytic vesicle membrane / fusion of virus membrane with host plasma membrane / suppression by virus of host type I interferon-mediated signaling pathway / fusion of virus membrane with host endosome membrane / viral envelope / viral entry into host cell / endoplasmic reticulum lumen / host cell plasma membrane / virion membrane / integral component of membrane / identical protein binding
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Spike glycoprotein, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 2 ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Spike glycoprotein, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome-related coronavirus / Homo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 29.3 Å
AuthorsBangaru S / Ward AB
Funding support United States, 2 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1170236 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)P01 AI110657 United States
CitationJournal: Cell Host Microbe / Year: 2021
Title: A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.
Authors: Hejun Liu / Meng Yuan / Deli Huang / Sandhya Bangaru / Fangzhu Zhao / Chang-Chun D Lee / Linghang Peng / Shawn Barman / Xueyong Zhu / David Nemazee / Dennis R Burton / Marit J van Gils / ...Authors: Hejun Liu / Meng Yuan / Deli Huang / Sandhya Bangaru / Fangzhu Zhao / Chang-Chun D Lee / Linghang Peng / Shawn Barman / Xueyong Zhu / David Nemazee / Dennis R Burton / Marit J van Gils / Rogier W Sanders / Hans-Christian Kornau / S Momsen Reincke / Harald Prüss / Jakob Kreye / Nicholas C Wu / Andrew B Ward / Ian A Wilson /
Abstract: Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking ...Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.
History
DepositionFeb 11, 2021-
Header (metadata) releaseMay 5, 2021-
Map releaseMay 5, 2021-
UpdateMay 26, 2021-
Current statusMay 26, 2021Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.018
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.018
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_23470.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationrefined map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.06 Å/pix.
x 256 pix.
= 527.36 Å
2.06 Å/pix.
x 256 pix.
= 527.36 Å
2.06 Å/pix.
x 256 pix.
= 527.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.06 Å
Density
Contour LevelBy AUTHOR: 0.018 / Movie #1: 0.018
Minimum - Maximum-0.03678865 - 0.08652344
Average (Standard dev.)-0.00015629629 (±0.0031824785)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 527.36 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z2.062.062.06
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z527.360527.360527.360
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ360360360
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-0.0370.087-0.000

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Supplemental data

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Sample components

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Entire : SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)

EntireName: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)
Components
  • Complex: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)
    • Complex: SARS-CoV spike glycoprotein
    • Complex: Fab CV38-142

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Supramolecule #1: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)

SupramoleculeName: SARS-CoV spike complexed with Fab CV38-142 (2 Fabs bound)
type: complex / ID: 1 / Parent: 0

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Supramolecule #2: SARS-CoV spike glycoprotein

SupramoleculeName: SARS-CoV spike glycoprotein / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Severe acute respiratory syndrome-related coronavirus
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: Fab CV38-142

SupramoleculeName: Fab CV38-142 / type: complex / ID: 3 / Parent: 1
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)

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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

Concentration0.02 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: Uranyl Formate
GridMaterial: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 29.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 5116

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