National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P50AI150476
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD020054
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
S10OD021741
United States
Citation
Journal: Cell / Year: 2021 Title: Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Authors: Daniel Asarnow / Bei Wang / Wen-Hsin Lee / Yuanyu Hu / Ching-Wen Huang / Bryan Faust / Patricia Miang Lon Ng / Eve Zi Xian Ngoh / Markus Bohn / David Bulkley / Andrés Pizzorno / Beatrice ...Authors: Daniel Asarnow / Bei Wang / Wen-Hsin Lee / Yuanyu Hu / Ching-Wen Huang / Bryan Faust / Patricia Miang Lon Ng / Eve Zi Xian Ngoh / Markus Bohn / David Bulkley / Andrés Pizzorno / Beatrice Ary / Hwee Ching Tan / Chia Yin Lee / Rabiatul Adawiyah Minhat / Olivier Terrier / Mun Kuen Soh / Frannie Jiuyi Teo / Yvonne Yee Chin Yeap / Shirley Gek Kheng Seah / Conrad En Zuo Chan / Emily Connelly / Nicholas J Young / Sebastian Maurer-Stroh / Laurent Renia / Brendon John Hanson / Manuel Rosa-Calatrava / Aashish Manglik / Yifan Cheng / Charles S Craik / Cheng-I Wang / Abstract: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by ...Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.
History
Deposition
Nov 14, 2020
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Header (metadata) release
May 26, 2021
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Map release
May 26, 2021
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Update
Oct 23, 2024
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Current status
Oct 23, 2024
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV / Details: 8-10 seconds, blot force 0.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 1 / Number real images: 7536 / Average exposure time: 5.9 sec. / Average electron dose: 67.7 e/Å2 Details: Movies were collected at super-resolution using correlated double sampling, with a frame time of 0.05 seconds and dose rate 8 e-/px/s
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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