National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01-AI138398-S1
United States
Citation
Journal: Cell / Year: 2020 Title: Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Authors: Christopher O Barnes / Anthony P West / Kathryn E Huey-Tubman / Magnus A G Hoffmann / Naima G Sharaf / Pauline R Hoffman / Nicholas Koranda / Harry B Gristick / Christian Gaebler / Frauke ...Authors: Christopher O Barnes / Anthony P West / Kathryn E Huey-Tubman / Magnus A G Hoffmann / Naima G Sharaf / Pauline R Hoffman / Nicholas Koranda / Harry B Gristick / Christian Gaebler / Frauke Muecksch / Julio C Cetrulo Lorenzi / Shlomo Finkin / Thomas Hägglöf / Arlene Hurley / Katrina G Millard / Yiska Weisblum / Fabian Schmidt / Theodora Hatziioannou / Paul D Bieniasz / Marina Caskey / Davide F Robbiani / Michel C Nussenzweig / Pamela J Bjorkman / Abstract: Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID- ...Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1 and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.
History
Deposition
Jun 8, 2020
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Header (metadata) release
Jul 1, 2020
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Map release
Jul 1, 2020
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Update
Sep 2, 2020
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Current status
Sep 2, 2020
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR / Details: 60 s glow discharge in air at 0.20 mA current
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV Details: 3 microliters added, blotted for 3 s with 0 blot force.
Details
Monodisperse sample taken after size-exclusion chromatography
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Electron microscopy
Microscope
FEI TITAN KRIOS
Details
Collected with 3x3 pattern and beam image shift
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 5940 / Average exposure time: 1.89 sec. / Average electron dose: 60.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
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