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- PDB-8r1c: SD1-2 Fab in complex with SARS-CoV-2 BA.2.12.1 Spike Glycoprotein -

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Basic information

Entry
Database: PDB / ID: 8r1c
TitleSD1-2 Fab in complex with SARS-CoV-2 BA.2.12.1 Spike Glycoprotein
Components
  • SD1-2 fab heavy chain
  • SD1-2 fab light chain
  • Spike glycoprotein,Fibritin
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike / Glycoprotein / Coronavirus / antibody / fab / SD1 domain / therapeutic / complex / neutralisingm convalescent sera / immune system / SD1-2 / BA.2.12.1 / omicron variant / virus / BA.2.86
Function / homology
Function and homology information


virion component / Maturation of spike protein / viral translation / Translation of Structural Proteins / host cell surface / Virion Assembly and Release / host extracellular space / symbiont-mediated-mediated suppression 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 / host cell surface / Virion Assembly and Release / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / 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
Fibritin C-terminal / Fibritin C-terminal region / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. ...Fibritin C-terminal / Fibritin C-terminal region / Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Spike glycoprotein / Fibritin
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
Enterobacteria phage T4 (virus)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å
AuthorsDuyvesteyn, H.M.E. / Ren, J. / Stuart, D.I.
Funding support United Kingdom, China, 4items
OrganizationGrant numberCountry
Wellcome Trust203141/A/16/Z United Kingdom
Wellcome Trust101122/Z/13/Z United Kingdom
Chinese Academy of Sciences2018-I2M-2-002 China
Medical Research Council (MRC, United Kingdom)MR/N00065X/1 United Kingdom
CitationJournal: Nat Commun / Year: 2024
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
DepositionNov 1, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 13, 2024Provider: repository / Type: Initial release
Revision 1.1Apr 10, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 6, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Spike glycoprotein,Fibritin
H: SD1-2 fab heavy chain
L: SD1-2 fab light chain
D: SD1-2 fab heavy chain
E: SD1-2 fab light chain
F: SD1-2 fab heavy chain
G: SD1-2 fab light chain
B: Spike glycoprotein,Fibritin
C: Spike glycoprotein,Fibritin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)509,05439
Polymers502,4189
Non-polymers6,63630
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Spike glycoprotein,Fibritin / S glycoprotein / E2 / Peplomer protein / Collar protein / Whisker antigen control protein


Mass: 142729.250 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2, (gene. exp.) Enterobacteria phage T4 (virus)
Gene: S, 2, wac / Production host: Homo sapiens (human) / References: UniProt: P0DTC2, UniProt: P10104
#2: Antibody SD1-2 fab heavy chain


Mass: 13274.797 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#3: Antibody SD1-2 fab light chain


Mass: 11468.586 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)
#4: Sugar...
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 30 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSourceDetails
1SD1-2 fab in complex with SARS-COV-2 BA.2.12.1 Spike GlycoproteinCOMPLEX#1-#30MULTIPLE SOURCES
2SD1-2 fabCOMPLEX#2-#31RECOMBINANTSequence from antibody isolated from convalescent sera.
3BA.2.12.1 Spike Glycoprotein EctodomainCOMPLEX#11RECOMBINANTHas fibritin oligomerization tag
Molecular weight
IDEntity assembly-IDExperimental value
11NO
22
33
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
11Severe acute respiratory syndrome coronavirus 22697049
22Homo sapiens (human)9606
33Severe acute respiratory syndrome coronavirus 22697049
43Enterobacteria phage T4 (virus)10665
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
11Homo sapiens (human)9606
22Homo sapiens (human)9606
33Homo sapiens (human)9606
Buffer solutionpH: 7.4
SpecimenConc.: 0.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Spike ectodomain incubated with SD1-2 fab in 2-fold molecular excess of sites (assuming three per trimeric spike unit).
Specimen supportDetails: Harrick Plasma unit. / Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: C-flat-2/1
VitrificationInstrument: 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
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Calibrated magnification: 165000 X / Nominal defocus max: 2600 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2EPUimage acquisition
4cryoSPARCCTF correction
7Cootmodel fitting
9cryoSPARCinitial Euler assignment
10cryoSPARCfinal Euler assignment
11cryoSPARCclassification
12cryoSPARC3D reconstruction
13PHENIXmodel refinement
CTF correctionDetails: Patch CTF and Motion correction, on-the-fly. / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 764482 / Details: Blob picker in cryoSPARC live interface.
SymmetryPoint symmetry: C3 (3 fold cyclic)
3D reconstructionResolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 503734 / Details: Estimation determined by cryoSPARC. / Symmetry type: POINT
Atomic model buildingB value: 68 / Protocol: RIGID BODY FIT / Space: REAL
Atomic model buildingPDB-ID: 8CIM

8cim


Accession code: 8CIM / Source name: PDB / Type: experimental model
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00831125
ELECTRON MICROSCOPYf_angle_d0.84942357
ELECTRON MICROSCOPYf_dihedral_angle_d5.0664326
ELECTRON MICROSCOPYf_chiral_restr0.0454887
ELECTRON MICROSCOPYf_plane_restr0.0055406

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