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- EMDB-22507: SARS-CoV-2 spike in complex with the S2H14 neutralizing antibody ... -

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Basic information

Entry
Database: EMDB / ID: EMD-22507
TitleSARS-CoV-2 spike in complex with the S2H14 neutralizing antibody Fab fragment (two receptor-binding domains open)
Map data
SampleSARS-CoV-2 spike in complex with the S2H14 neutralizing antibody Fab fragment (two receptor-binding domains open)
  • spike glycoproteinSpike protein
  • S2H14 neutralizing antibody Fab fragment
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 7.8 Å
AuthorsPark YJ / Tortorici MA / Walls AC / Czudnochowski N / Seattle Structural Genomics Center for Infectious Disease (SSGCID) / Snell G / Veesler D
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM120553 United States
CitationJournal: Cell / Year: 2020
Title: Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology.
Authors: Luca Piccoli / Young-Jun Park / M Alejandra Tortorici / Nadine Czudnochowski / Alexandra C Walls / Martina Beltramello / Chiara Silacci-Fregni / Dora Pinto / Laura E Rosen / John E Bowen / ...Authors: Luca Piccoli / Young-Jun Park / M Alejandra Tortorici / Nadine Czudnochowski / Alexandra C Walls / Martina Beltramello / Chiara Silacci-Fregni / Dora Pinto / Laura E Rosen / John E Bowen / Oliver J Acton / Stefano Jaconi / Barbara Guarino / Andrea Minola / Fabrizia Zatta / Nicole Sprugasci / Jessica Bassi / Alessia Peter / Anna De Marco / Jay C Nix / Federico Mele / Sandra Jovic / Blanca Fernandez Rodriguez / Sneha V Gupta / Feng Jin / Giovanni Piumatti / Giorgia Lo Presti / Alessandra Franzetti Pellanda / Maira Biggiogero / Maciej Tarkowski / Matteo S Pizzuto / Elisabetta Cameroni / Colin Havenar-Daughton / Megan Smithey / David Hong / Valentino Lepori / Emiliano Albanese / Alessandro Ceschi / Enos Bernasconi / Luigia Elzi / Paolo Ferrari / Christian Garzoni / Agostino Riva / Gyorgy Snell / Federica Sallusto / Katja Fink / Herbert W Virgin / Antonio Lanzavecchia / Davide Corti / David Veesler /
Abstract: Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. ...Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.
History
DepositionAug 20, 2020-
Header (metadata) releaseOct 14, 2020-
Map releaseOct 14, 2020-
UpdateDec 2, 2020-
Current statusDec 2, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.3
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.3
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_22507.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.16 Å/pix.
x 400 pix.
= 464. Å
1.16 Å/pix.
x 400 pix.
= 464. Å
1.16 Å/pix.
x 400 pix.
= 464. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.16 Å
Density
Contour LevelBy AUTHOR: 0.3 / Movie #1: 0.3
Minimum - Maximum-0.59964275 - 1.5186515
Average (Standard dev.)0.0031053708 (±0.033320554)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 464.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.161.161.16
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z464.000464.000464.000
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ360360360
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-0.6001.5190.003

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Supplemental data

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Additional map: Unsharpened map

Fileemd_22507_additional_1.map
AnnotationUnsharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire SARS-CoV-2 spike in complex with the S2H14 neutralizing antibody ...

EntireName: SARS-CoV-2 spike in complex with the S2H14 neutralizing antibody Fab fragment (two receptor-binding domains open)
Number of Components: 3

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Component #1: protein, SARS-CoV-2 spike in complex with the S2H14 neutralizing ...

ProteinName: SARS-CoV-2 spike in complex with the S2H14 neutralizing antibody Fab fragment (two receptor-binding domains open)
Recombinant expression: No

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Component #2: protein, spike glycoprotein

ProteinName: spike glycoproteinSpike protein / Recombinant expression: No
SourceSpecies: Severe acute respiratory syndrome coronavirus 2
Source (engineered)Expression System: Homo sapiens (human)

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Component #3: protein, S2H14 neutralizing antibody Fab fragment

ProteinName: S2H14 neutralizing antibody Fab fragment / Recombinant expression: No
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Cricetulus griseus (Chinese hamster)

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Experimental details

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Sample preparation

SpecimenSpecimen State: Particle / Method: cryo EM
Sample solutionpH: 8
Support filmunspecified
VitrificationCryogen Name: ETHANE

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Electron microscopy imaging

ImagingMicroscope: TFS GLACIOS
Electron gunElectron Source: FIELD EMISSION GUN / Accelerating Voltage: 200 kV / Electron Dose: 60 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: C1 (asymmetric) / Number of Projections: 9957
3D reconstructionSoftware: cryoSPARC / Resolution: 7.8 Å / Resolution Method: FSC 0.143 CUT-OFF

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