+Open data
-Basic information
Entry | Database: PDB / ID: 7ntc | ||||||
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Title | Trimeric SARS-CoV-2 spike ectodomain bound to P008_056 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / spike / biliverdin / COVID19 / Antibody / Fab / epitope / NTD | ||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
Authors | Rosa, A. / Pye, V.E. / Nans, A. / Cherepanov, P. | ||||||
Funding support | United Kingdom, 1items
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Citation | 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ntc.cif.gz | 675.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ntc.ent.gz | 561.7 KB | Display | PDB format |
PDBx/mmJSON format | 7ntc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ntc_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
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Full document | 7ntc_full_validation.pdf.gz | 2.7 MB | Display | |
Data in XML | 7ntc_validation.xml.gz | 114.5 KB | Display | |
Data in CIF | 7ntc_validation.cif.gz | 171.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nt/7ntc ftp://data.pdbj.org/pub/pdb/validation_reports/nt/7ntc | HTTPS FTP |
-Related structure data
Related structure data | 12587MC 7b62C 7nt9C 7ntaC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Antibody , 2 types, 2 molecules HL
#2: Antibody | Mass: 27239.400 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human) |
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#3: Antibody | Mass: 25253.180 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): Expi293 / Production host: Homo sapiens (human) |
-Protein / Non-polymers , 2 types, 5 molecules ABC
#1: Protein | Mass: 142269.859 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Cell (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #5: Chemical | |
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-Sugars , 2 types, 54 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 0.47886 MDa / Experimental value: NO | ||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 Details: 150 mM NaCl, 1 mM ethylenediaminetetraacetic acid (EDTA), 25 mM Tris-HCl, pH 8.0 | ||||||||||||||||||||||||||||
Specimen | Conc.: 0.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: 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 | ||||||||||||||||||||||||||||
Specimen support | Grid type: Quantifoil R2/2 | ||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 51 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 17010 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. |
-Processing
Software | Name: PHENIX / Version: 1.19rc5_4047: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 78291 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL Details: in addition to the spike: 6APC and 6PHB were used as templates for the heavy and light chains of the Fab respectively | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 6ZGE | ||||||||||||||||||||||||
Refine LS restraints |
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