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- PDB-8r1d: SD1-3 Fab in complex with SARS-CoV-2 BA.2.12.1 Spike Glycoprotein -
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Open data
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Basic information
Entry | Database: PDB / ID: 8r1d | |||||||||||||||
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Title | SD1-3 Fab in complex with SARS-CoV-2 BA.2.12.1 Spike Glycoprotein | |||||||||||||||
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![]() | VIRAL PROTEIN / SARS-CoV-2 / Spike / Glycoprotein / Coronavirus / antibody / Fab / SD1 domain / therapeutic / complex / neutralisingm convalescent sera / immune system / SD1-3 / BA.2.12.1 / omicron variant / virus / BA.2.86 | |||||||||||||||
Function / homology | ![]() virion component / 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 ...virion component / 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 | ![]() ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.37 Å | |||||||||||||||
![]() | Duyvesteyn, H.M.E. / Ren, J. / Stuart, D.I. | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86. Authors: Daming Zhou / Piyada Supasa / Chang Liu / Aiste Dijokaite-Guraliuc / Helen M E Duyvesteyn / Muneeswaran Selvaraj / Alexander J Mentzer / Raksha Das / Wanwisa Dejnirattisai / Nigel Temperton ...Authors: Daming Zhou / Piyada Supasa / Chang Liu / Aiste Dijokaite-Guraliuc / Helen M E Duyvesteyn / Muneeswaran Selvaraj / Alexander J Mentzer / Raksha Das / Wanwisa Dejnirattisai / Nigel Temperton / Paul Klenerman / Susanna J Dunachie / Elizabeth E Fry / Juthathip Mongkolsapaya / Jingshan Ren / David I Stuart / Gavin R Screaton / ![]() ![]() ![]() Abstract: Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed ...Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 763.3 KB | Display | ![]() |
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PDB format | ![]() | 616.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 18808MC ![]() 8cinC ![]() 8r1cC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Antibody | Mass: 12914.263 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Antibody | Mass: 11218.331 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Protein | Mass: 142729.250 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2, wac / Production host: ![]() #4: Sugar | ChemComp-NAG / #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
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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 |
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Sample preparation
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||
Specimen | Conc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Spike ectodomain incubated with SD1-3 fab in 2-fold molecular excess of sites (assuming three per trimeric spike unit). | ||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: C-flat-2/1 | ||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.5 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 165000 X / Nominal defocus max: 2700 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
EM software |
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CTF correction | Details: Patch CTF and Motion correction, on-the-fly. / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3282771 / Details: Blob picker in cryoSPARC live interface. | ||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.37 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 167816 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 8CIM Accession code: 8CIM / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||
Refine LS restraints |
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