Journal: Sci Adv / Year: 2021 Title: SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity. Authors: Annachiara Rosa / Valerie E Pye / Carl Graham / Luke Muir / Jeffrey Seow / Kevin W Ng / Nicola J Cook / Chloe Rees-Spear / Eleanor Parker / Mariana Silva Dos Santos / Carolina Rosadas / ...Authors: Annachiara Rosa / Valerie E Pye / Carl Graham / Luke Muir / Jeffrey Seow / Kevin W Ng / Nicola J Cook / Chloe Rees-Spear / Eleanor Parker / Mariana Silva Dos Santos / Carolina Rosadas / Alberto Susana / Hefin Rhys / Andrea Nans / Laura Masino / Chloe Roustan / Evangelos Christodoulou / Rachel Ulferts / Antoni G Wrobel / Charlotte-Eve Short / Michael Fertleman / Rogier W Sanders / Judith Heaney / Moira Spyer / Svend Kjær / Andy Riddell / Michael H Malim / Rupert Beale / James I MacRae / Graham P Taylor / Eleni Nastouli / Marit J van Gils / Peter B Rosenthal / Massimo Pizzato / Myra O McClure / Richard S Tedder / George Kassiotis / Laura E McCoy / Katie J Doores / Peter Cherepanov / Abstract: The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme ...The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme metabolism, with nanomolar affinity. Using cryo-electron microscopy and x-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.
History
Deposition
Mar 9, 2021
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Header (metadata) release
Apr 28, 2021
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Map release
Apr 28, 2021
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Update
Jun 9, 2021
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Current status
Jun 9, 2021
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Supramolecule #1: Stabilised SARS-CoV-2 spike ectodomain trimer bound to one P008_0...
Supramolecule
Name: Stabilised SARS-CoV-2 spike ectodomain trimer bound to one P008_056 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 Details: natural source below: Spike is SARS-Cov-2 and Fab is Human - there is only option for one natural source below!
SARS-CoV-2 spike ectodomain (0.6 mg/ml final concentration in TBSE supplemented with 0.1% n-octylglucoside) with 0.2 mg/ml P008_056 Fab
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 17010 / Average electron dose: 51.0 e/Å2 Details: A total of 17010 movies were collected with a pixel size of 1.38 Angstrom and total electron exposure of 51 electrons per square Angstrom, spread over 40 frames.
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
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Image processing
Final reconstruction
Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 2) / Number images used: 78291
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