Journal: Nat Commun / Year: 2022 Title: Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes. Authors: Chunyan Wang / Emma L Hesketh / Tatiana M Shamorkina / Wentao Li / Peter J Franken / Dubravka Drabek / Rien van Haperen / Sarah Townend / Frank J M van Kuppeveld / Frank Grosveld / Neil A ...Authors: Chunyan Wang / Emma L Hesketh / Tatiana M Shamorkina / Wentao Li / Peter J Franken / Dubravka Drabek / Rien van Haperen / Sarah Townend / Frank J M van Kuppeveld / Frank Grosveld / Neil A Ranson / Joost Snijder / Raoul J de Groot / Daniel L Hurdiss / Berend-Jan Bosch / Abstract: Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus ...Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1 domain, but, remarkably, also to S1. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1 epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.
Entire : Human coronavirus OC43 spike glycoprotein ectodomain in complex w...
Entire
Name: Human coronavirus OC43 spike glycoprotein ectodomain in complex with the 43E6 antibody Fab fragment
Components
Complex: Human coronavirus OC43 spike glycoprotein ectodomain in complex with the 43E6 antibody Fab fragment
Protein or peptide: 43E6 antibody heavy chain
Protein or peptide: 43E6 antibody light chain
Protein or peptide: Spike glycoprotein
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
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Supramolecule #1: Human coronavirus OC43 spike glycoprotein ectodomain in complex w...
Supramolecule
Name: Human coronavirus OC43 spike glycoprotein ectodomain in complex with the 43E6 antibody Fab fragment type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)
Organism: Human coronavirus OC43 / Strain: USA/1967
Recombinant expression
Organism: Homo sapiens (human) / Recombinant cell: HEK293T
Molecular weight
Theoretical: 583 KDa
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Macromolecule #1: 43E6 antibody heavy chain
Macromolecule
Name: 43E6 antibody heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV
Details
Purified OC43 spike ectodomain and the antibody Fab fragments were incubated together for 5 minutes at a 1:1 molar ratio
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Electron microscopy
Microscope
TFS KRIOS
Details
A 30 degree stage tilt was employed during data collection to increase the number of side views visualised due to preferential orientation.
Image recording
Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 1 / Number real images: 837 / Average exposure time: 60.0 sec. / Average electron dose: 52.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Type of model: INSILICO MODEL In silico model: The UCSF Chimera molmap command was used to generate a 50 angstrom resolution starting model from the OC43 spike model (6OHW).
Final reconstruction
Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1.1) / Number images used: 53157
Initial angle assignment
Type: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 3.0.1)
Final angle assignment
Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1.1)
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